Cardiolipin remodeling by ALCAT1 links hypoxia to coronary artery disease by promoting mitochondrial dysfunction.

ABSTRACT: Cardiolipin is a mitochondrial signature phospholipid that plays a pivotal role in maintaining cardiac health. A loss of tetralinoleoyl cardiolipin (TLCL), the predominant cardiolipin species in the healthy mammalian heart, is implicated in the pathogenesis of coronary heart disease (CHD) through poorly defined mechanisms. Here, we identified acyl-coenzyme A:lysocardiolipin acyltransferase-1 (ALCAT1) as the missing link between hypoxia and CHD in an animal model of myocardial infarction (MI). ALCAT1 is an acyltransferase that promotes mitochondrial dysfunction in aging-related diseases by catalyzing pathological remodeling of cardiolipin. In support of a causative role of ALCAT1 in CHD, we showed that ALCAT1 expression was potently upregulated by MI, linking myocardial hypoxia to oxidative

SUBMITTER: Jia D 

PROVIDER: S-EPMC8636157 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature