PLIN5 interacts with FATP4 at membrane contact sites to promote lipid droplet-to-mitochondria fatty acid transport.

Autor:	Miner GE; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., So CM; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Edwards W; Department of Biology and Genetics, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Ragusa JV; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Wine JT; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA., Wong Gutierrez D; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA., Airola MV; Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794, USA., Herring LE; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Coleman RA; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Klett EL; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA., Cohen S; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: sarahcoh@med.unc.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2023 Jul 24; Vol. 58 (14), pp. 1250-1265.e6. Date of Electronic Publication: 2023 Jun 07.
DOI:	10.1016/j.devcel.2023.05.006
Abstrakt:	Cells adjust their metabolism by remodeling membrane contact sites that channel metabolites to different fates. Lipid droplet (LD)-mitochondria contacts change in response to fasting, cold exposure, and exercise. However, their function and mechanism of formation have remained controversial. We focused on perilipin 5 (PLIN5), an LD protein that tethers mitochondria, to probe the function and regulation of LD-mitochondria contacts. We demonstrate that efficient LD-to-mitochondria fatty acid (FA) trafficking and ß-oxidation during starvation of myoblasts are promoted by phosphorylation of PLIN5 and require an intact PLIN5 mitochondrial tethering domain. Using human and murine cells, we further identified the acyl-CoA synthetase, FATP4 (ACSVL4), as a mitochondrial interactor of PLIN5. The C-terminal domains of PLIN5 and FATP4 constitute a minimal protein interaction capable of inducing organelle contacts. Our work suggests that starvation leads to phosphorylation of PLIN5, lipolysis, and subsequent channeling of FAs from LDs to FATP4 on mitochondria for conversion to fatty-acyl-CoAs and subsequent oxidation. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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