Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast
Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, w...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Malecki, Michal [verfasserIn] Kamrad, Stephan [verfasserIn] Ralser, Markus [verfasserIn] Bähler, Jürg [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Anmerkung: |
© The Author(s) 2020 |
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| Übergeordnetes Werk: |
Enthalten in: EMBO Reports - Nature Publishing Group UK, 2023, 21(2020), 11 vom: 07. Sept. |
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| Übergeordnetes Werk: |
volume:21 ; year:2020 ; number:11 ; day:07 ; month:09 |
| Links: |
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| DOI / URN: |
10.15252/embr.202050845 |
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| Katalog-ID: |
SPR058120815 |
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| 520 | |a Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. | ||
| 520 | |a Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. | ||
| 520 | |a Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. | ||
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10.15252/embr.202050845 doi (DE-627)SPR058120815 (SPR)embr.202050845-e DE-627 ger DE-627 rakwb eng Malecki, Michal verfasserin (orcid)0000-0002-1525-5036 aut Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. arginine (dpeaa)DE-He213 cellular metabolism (dpeaa)DE-He213 fermentation (dpeaa)DE-He213 respiration (dpeaa)DE-He213 Kamrad, Stephan verfasserin (orcid)0000-0002-5957-4661 aut Ralser, Markus verfasserin aut Bähler, Jürg verfasserin (orcid)0000-0003-4036-1532 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 11 vom: 07. Sept. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:11 day:07 month:09 https://dx.doi.org/10.15252/embr.202050845 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 11 07 09 |
| spelling |
10.15252/embr.202050845 doi (DE-627)SPR058120815 (SPR)embr.202050845-e DE-627 ger DE-627 rakwb eng Malecki, Michal verfasserin (orcid)0000-0002-1525-5036 aut Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. arginine (dpeaa)DE-He213 cellular metabolism (dpeaa)DE-He213 fermentation (dpeaa)DE-He213 respiration (dpeaa)DE-He213 Kamrad, Stephan verfasserin (orcid)0000-0002-5957-4661 aut Ralser, Markus verfasserin aut Bähler, Jürg verfasserin (orcid)0000-0003-4036-1532 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 11 vom: 07. Sept. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:11 day:07 month:09 https://dx.doi.org/10.15252/embr.202050845 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 11 07 09 |
| allfields_unstemmed |
10.15252/embr.202050845 doi (DE-627)SPR058120815 (SPR)embr.202050845-e DE-627 ger DE-627 rakwb eng Malecki, Michal verfasserin (orcid)0000-0002-1525-5036 aut Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. arginine (dpeaa)DE-He213 cellular metabolism (dpeaa)DE-He213 fermentation (dpeaa)DE-He213 respiration (dpeaa)DE-He213 Kamrad, Stephan verfasserin (orcid)0000-0002-5957-4661 aut Ralser, Markus verfasserin aut Bähler, Jürg verfasserin (orcid)0000-0003-4036-1532 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 11 vom: 07. Sept. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:11 day:07 month:09 https://dx.doi.org/10.15252/embr.202050845 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 11 07 09 |
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10.15252/embr.202050845 doi (DE-627)SPR058120815 (SPR)embr.202050845-e DE-627 ger DE-627 rakwb eng Malecki, Michal verfasserin (orcid)0000-0002-1525-5036 aut Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. arginine (dpeaa)DE-He213 cellular metabolism (dpeaa)DE-He213 fermentation (dpeaa)DE-He213 respiration (dpeaa)DE-He213 Kamrad, Stephan verfasserin (orcid)0000-0002-5957-4661 aut Ralser, Markus verfasserin aut Bähler, Jürg verfasserin (orcid)0000-0003-4036-1532 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 11 vom: 07. Sept. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:11 day:07 month:09 https://dx.doi.org/10.15252/embr.202050845 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 11 07 09 |
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10.15252/embr.202050845 doi (DE-627)SPR058120815 (SPR)embr.202050845-e DE-627 ger DE-627 rakwb eng Malecki, Michal verfasserin (orcid)0000-0002-1525-5036 aut Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2020 Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. arginine (dpeaa)DE-He213 cellular metabolism (dpeaa)DE-He213 fermentation (dpeaa)DE-He213 respiration (dpeaa)DE-He213 Kamrad, Stephan verfasserin (orcid)0000-0002-5957-4661 aut Ralser, Markus verfasserin aut Bähler, Jürg verfasserin (orcid)0000-0003-4036-1532 aut Enthalten in EMBO Reports Nature Publishing Group UK, 2023 21(2020), 11 vom: 07. Sept. (DE-627)320645622 (DE-600)2025376-X 1469-3178 nnns volume:21 year:2020 number:11 day:07 month:09 https://dx.doi.org/10.15252/embr.202050845 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_72 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_168 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_211 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_252 GBV_ILN_266 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4029 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4116 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4155 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4311 GBV_ILN_4313 GBV_ILN_4314 GBV_ILN_4318 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4598 GBV_ILN_4700 AR 21 2020 11 07 09 |
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Enthalten in EMBO Reports 21(2020), 11 vom: 07. Sept. volume:21 year:2020 number:11 day:07 month:09 |
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Malecki, Michal @@aut@@ Kamrad, Stephan @@aut@@ Ralser, Markus @@aut@@ Bähler, Jürg @@aut@@ |
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| author |
Malecki, Michal |
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Malecki, Michal misc arginine misc cellular metabolism misc fermentation misc respiration Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast |
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Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast arginine (dpeaa)DE-He213 cellular metabolism (dpeaa)DE-He213 fermentation (dpeaa)DE-He213 respiration (dpeaa)DE-He213 |
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Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast |
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Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast |
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Malecki, Michal |
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Malecki, Michal Kamrad, Stephan Ralser, Markus Bähler, Jürg |
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Malecki, Michal |
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10.15252/embr.202050845 |
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mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast |
| title_auth |
Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast |
| abstract |
Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. © The Author(s) 2020 |
| abstractGer |
Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. © The Author(s) 2020 |
| abstract_unstemmed |
Abstract When glucose is available, many organisms repress mitochondrial respiration in favour of aerobic glycolysis, or fermentation in yeast, that suffices for ATP production. Fission yeast cells, however, rely partially on respiration for rapid proliferation under fermentative conditions. Here, we determined the limiting factors that require respiratory function during fermentation. When inhibiting the electron transport chain, supplementation with arginine was necessary and sufficient to restore rapid proliferation. Accordingly, a systematic screen for mutants growing poorly without arginine identified mutants defective in mitochondrial oxidative metabolism. Genetic or pharmacological inhibition of respiration triggered a drop in intracellular levels of arginine and amino acids derived from the Krebs cycle metabolite alpha‐ketoglutarate: glutamine, lysine and glutamic acid. Conversion of arginine into these amino acids was required for rapid proliferation when blocking the respiratory chain. The respiratory block triggered an immediate gene expression response diagnostic of TOR inhibition, which was muted by arginine supplementation or without the AMPK‐activating kinase Ssp1. The TOR‐controlled proteins featured biased composition of amino acids reflecting their shortage after respiratory inhibition. We conclude that respiration supports rapid proliferation in fermenting fission yeast cells by boosting the supply of Krebs cycle‐derived amino acids. Synopsis Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. Inhibition of the respiratory chain reduces growth and intracellular amino‐acid concentrations, most notably arginine.Arginine supplementation, and its catabolism into amino acids that are normally derived from alpha‐ketoglutarate, are sufficient to restore rapid growth.Inhibition of the respiratory chain also triggers a gene‐expression response through TOR inhibition, and the regulated proteins show biased amino‐acid compositions reflecting their shortage in this condition. Graphical Abstract Mitochondrial respiration is required for rapid fermentative proliferation of fission yeast cells by supplying amino‐acid derivatives of the Krebs‐cycle metabolite alpha‐ketoglutarate. © The Author(s) 2020 |
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11 |
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Mitochondrial respiration is required to provide amino acids during fermentative proliferation of fission yeast |
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https://dx.doi.org/10.15252/embr.202050845 |
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Kamrad, Stephan Ralser, Markus Bähler, Jürg |
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10.15252/embr.202050845 |
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2024-10-26T05:40:04.328Z |
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| score |
7.4008236 |