Mitochondrial Calcium Regulates Lipid Metabolism By Modulating Tethering of Mitochondria to Lipid Droplets

ABSTRACT: Adrenergic stimulation of brown adipocytes induces a robust detachment of mitochondria from LD that is followed by lipolysis and lipid catabolism. However, the signals inducing attachment or detachment, and their role in lipid metabolism, remain unknown. Here, we reconstituted BAT mitochondria-LD interaction ex vivo. We find that removal of mitochondria from LDs permits higher lipolytic activity of recombinant lipases. Testing the effect of thermogenic secondary messengers and metabolites on attachment and detachment identified elevated mitochondrial matrix Ca2+ as a potent inducer of detachment. Deletion of the mitochondrial sodium/calcium exchanger, NCLX, resulted in reduced attachment and increased detachment, while activation of NCLX increased attachment in vivo and in vitro. We find

SUBMITTER: Orian, S. Shirihai 

PROVIDER: S-SCDT-10_1038-S44318-026-00827-8 | biostudies-other |

REPOSITORIES: biostudies-other