Dataset Information

Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria

ABSTRACT: Cells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by fatty acid synthase, FASN) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially in higher eukaryotes, with the major product(s), metabolic roles, and cellular function(s) being essentially unknown. Here we show that hypomorphic mtFAS mutant mouse skeletal myoblast cell lines display a severe loss of electron transport chain (ETC) complexes and exhibit compensatory metabolic activities including reductive carboxylation. This effect on ETC complexes appears to be independent of protein lipoylation, the best characterized function of mtFAS, as mutants lacking lipoylation have an intact ETC. Finally, mtFAS impairment blocks the differentiation of skeletal myoblasts in vitro. Together, these data suggest that ETC activity in mammals is profoundly controlled by mtFAS function, thereby connecting anabolic fatty acid synthesis with the oxidation of carbon fuels.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Joao Paulo

LAB HEAD: Steven P. Gygi

PROVIDER: PXD021034 | Pride | 2020-09-02

REPOSITORIES: Pride

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			Action	DRS
	353755_m17346_ftMAS_TMT_Frac2.mzIdentML	Mzid
	353756_m17350_ftMAS_TMT_Frac6.mzIdentML	Mzid
	353757_m17349_ftMAS_TMT_Frac5.mzIdentML	Mzid
	353758_m17348_ftMAS_TMT_Frac4.mzIdentML	Mzid
	353759_m17347_ftMAS_TMT_Frac3.mzIdentML	Mzid

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Publications

Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria.

Nowinski Sara M SM Solmonson Ashley A Rusin Scott F SF Maschek J Alan JA Bensard Claire L CL Fogarty Sarah S Jeong Mi-Young MY Lettlova Sandra S Berg Jordan A JA Morgan Jeffrey T JT Ouyang Yeyun Y Naylor Bradley C BC Paulo Joao A JA Funai Katsuhiko K Cox James E JE Gygi Steven P SP Winge Dennis R DR DeBerardinis Ralph J RJ Rutter Jared J

eLife 20200817

Cells harbor two systems for fatty acid synthesis, one in the cytoplasm (catalyzed by fatty acid synthase, FASN) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, especially in higher eukaryotes, with the major product(s), metabolic roles, and cellular function(s) being essentially unknown. Here we show that hypomorphic mtFAS mutant mouse skeletal myoblast cell lines display a severe loss of electron transport chain (ETC) complexes and exhibit compensatory ...[more]

PMID: 32804083

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