PLX057557

GSE148617: Mitochondrial fatty acid synthesis coordinates mitochondrial oxidative metabolism

  • Organsim mouse
  • Type RNASEQ
  • Target gene
  • Project ARCHS4

Cells harbor two systems for the synthesis of fatty acids, one in the cytoplasm (FASN or fatty acid synthase) and one in the mitochondria (mtFAS). In contrast to FASN, mtFAS is poorly characterized, with the major product(s), metabolic roles, and cellular function(s) essentially unknown. Here we show that hypomorphic mtFAS mutants display a profound loss of electron transport chain (ETC) complexes and exhibit compensatory reductive carboxylation. This effect on ETC complexes is independent of the synthesis of lipoic acid, the best characterized function of mtFAS, as mutants lacking lipoic acid synthesis have an intact ETC. Finally, mtFAS impairment blocks the differentiation of skeletal myoblasts in vitro. 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. SOURCE: Jeff Morgan (jeff.morgan@biochem.utah.edu) - Jared Rutter University of Utah

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