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Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria.

Sara M Nowinski | Ashley Solmonson | Scott F Rusin | J Alan Maschek | Claire L Bensard | Sarah Fogarty | Mi-Young Jeong | Sandra Lettlova | Jordan A Berg | Jeffrey T Morgan | Yeyun Ouyang | Bradley C Naylor | Joao A Paulo | Katsuhiko Funai | James E Cox | Steven P Gygi | Dennis R Winge | Ralph J DeBerardinis | Jared Rutter
eLife | 2020

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.

Pubmed ID: 32804083 RIS Download

Antibodies used in this publication

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: GM97645
  • Agency: NIH HHS, United States
    Id: S10 OD016232
  • Agency: NIGMS NIH HHS, United States
    Id: R35 GM131854
  • Agency: NIH HHS, United States
    Id: S10 OD018210
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM115174
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM110755
  • Agency: NCI NIH HHS, United States
    Id: R35 CA220449
  • Agency: NIA NIH HHS, United States
    Id: R21 AG063077
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007576
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM132129
  • Agency: NCI NIH HHS, United States
    Id: R35CA22044901
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK107397
  • Agency: NIDDK NIH HHS, United States
    Id: U54 DK110858
  • Agency: NICHD NIH HHS, United States
    Id: F32 HD096786
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM067945
  • Agency: NIDDK NIH HHS, United States
    Id: T32DK11096601
  • Agency: NIH HHS, United States
    Id: S10 OD021505
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM115129

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