MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme
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s41467-020-18607-1.pdf
Description
Published version
Size
2.75 MB
Format
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Checksum (MD5)
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Author(s)
Li, Yingzhong
Ivica, Nikola A
Dong, Ting
Papageorgiou, Dimitrios P
He, Yanpu
Brown, Douglas R
Kleyman, Marianna
Hu, Guangan
Chen, Walter W
Sullivan, Lucas B
Date Issued
2020
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Li, Yingzhong, Ivica, Nikola A, Dong, Ting, Papageorgiou, Dimitrios P, He, Yanpu et al. 2020. "MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme." Nature Communications, 11 (1).
Version
Final published version
Abstract
© 2020, The Author(s). ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these outputs are regulated to balance the cellular requirement for energy and heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples mitochondrial respiration to switch ATP synthesis to thermogenesis in response to heme. When heme levels are low, MSFD7C promotes ATP synthesis by interacting with components of the electron transport chain (ETC) complexes III, IV, and V, and destabilizing sarcoendoplasmic reticulum Ca2+-ATPase 2b (SERCA2b). Upon heme binding to the N-terminal domain, MFSD7C dissociates from ETC components and SERCA2b, resulting in SERCA2b stabilization and thermogenesis. The heme-regulated switch between ATP synthesis and thermogenesis enables cells to match outputs of mitochondrial respiration to their metabolic state and nutrient supply, and represents a cell intrinsic mechanism to regulate mitochondrial energy metabolism.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Materials Science and Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Whitehead Institute for Biomedical Research
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/S41467-020-18607-1
