biostudies-literatureLabbe KNational Cancer InstituteNational Institutes of HealthCanadian Institutes of Health Researche202103122https://www.ebi.ac.uk/biostudies/studies/S-EPMC8496048biostudies-literatureUnknown220(11)Mitochondrial function is integrated with cellular status through the regulation of opposing mitochondrial fusion and division events. Here we uncover a link between mitochondrial dynamics and lipid metabolism by examining the cellular role of mitochondrial carrier homologue 2 (MTCH2). MTCH2 is a modified outer mitochondrial membrane carrier protein implicated in intrinsic cell death and in the in vivo regulation of fatty acid metabolism. Our data indicate that MTCH2 is a selective effector of starvation-induced mitochondrial hyperfusion, a cytoprotective response to nutrient deprivation. We find that MTCH2 stimulates mitochondrial fusion in a manner dependent on the bioactive lipogenesis intermediate lysophosphatidic acid. We propose that MTCH2 monitors flux through the lipogenesis pathwaThe Journal of cell biologyThe modified mitochondrial outer membrane carrier MTCH2 links mitochondrial fusion to lipogenesis.PMC84960481S10RR024543-01P30CA093373R01GM126081R37GM097432S10OD021801Lerner CLe Vasseur MLabbe KNunnari JMookerjee SGibbs EfalseThe modified mitochondrial outer membrane carrier MTCH2 links mitochondrial fusion to lipogenesis.Mitochondrial function is integrated with cellular status through the regulation of opposing mitochondrial fusion and division events. Here we uncover a link between mitochondrial dynamics and lipid metabolism by examining the cellular role of mitochondrial carrier homologue 2 (MTCH2). MTCH2 is a modified outer mitochondrial membrane carrier protein implicated in intrinsic cell death and in the in vivo regulation of fatty acid metabolism. Our data indicate that MTCH2 is a selective effector of starvation-induced mitochondrial hyperfusion, a cytoprotective response to nutrient deprivation. We find that MTCH2 stimulates mitochondrial fusion in a manner dependent on the bioactive lipogenesis intermediate lysophosphatidic acid. We propose that MTCH2 monitors flux through the lipogenesis pathwa2021-01-01T00:00:00Z2021 Nov2025-04-05T14:05:35.217Z2025-04-05T14:05:35.217ZS-EPMC84960483458634610.1083/jcb.202103122