@article{29ef720e49924413a42777d149f66011,
title = "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.",
author = "Nowinski, {Sara M.} and Ashley Solmonson and Rusin, {Scott F.} and Maschek, {J. Alan} and Bensard, {Claire L.} and Sarah Fogarty and Jeong, {Mi Young} and Sandra Lettlova and Berg, {Jordan A.} and Morgan, {Jeffrey T.} and Yeyun Ouyang and Naylor, {Bradley C.} and Paulo, {Joao A.} and Katsuhiko Funai and Cox, {James E.} and Gygi, {Steven P.} and Winge, {Dennis R.} and Deberardinis, {Ralph J.} and Jared Rutter",
note = "Funding Information: The authors are grateful to members of the Department of Biochemistry at the University of Utah for useful discussion and feedback, specifically Chintan Kikani, Gabrielle Kardon, and Dana Carroll. Cloning of CRISPR plasmids was done by the Mutation Generation and Detection Core at the University of Utah. FACS to generate single cell clones was done in the Flow Cytometry Core at the University of Utah. Flux lipidomics and analysis was performed at the Metabolomics Core Facility at the University of Utah. RNA-Seq library preparation and sequencing was performed by the High-Throughput Genomics Shared Resource at the Huntsman Cancer Institute. The support and resources from the Center for High Performance Computing at the University of Utah are gratefully acknowledged. This study was supported by grants from the NIH (GM115174 and GM115129 to JR, GM110755 to DW) and the Nora Eccles Treadwell Foundation (to JR), as well as HHMI (JR). Support for SMN was also provided by UMDF and ACS postdoctoral fellowships, along with T32HL007576. JAB received support from NIDDK T32DK11096601 to Wendy W Chapman and Simon J Fisher. RJD is an advisor for Agios Pharmaceuticals and is supported by HHMI, NCI (R35CA22044901) and the Once Upon a Time Foundation. AS is funded by NICHD (F32HD096786). KF is funded by R01DK107397 and R21AG063077. JEC is funded by S10OD016232, S10OD021505, and U54DK110858. JAP is funded by NIH/NIGMS grant R01 GM132129 and SPG is funded by GM97645. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} Nowinski et al.",
year = "2020",
month = aug,
doi = "10.7554/ELIFE.58041",
language = "English (US)",
volume = "9",
pages = "1--35",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}