Lysocardiolipin acyltransferase 1 (ALCAT1) controls mitochondrial DNA fidelity and biogenesis through modulation of MFN2 expression

摘要: Oxidative stress causes mitochondrial fragmentation and dysfunction in age-related diseases through unknown mechanisms. Cardiolipin (CL) is a phospholipid required for oxidative phosphorylation. The function of CL determined by its acyl composition, which significantly altered the onset diseases. Here, we examine role acyl-CoA:lysocardiolipin acyltransferase lysocardiolipin 1 (ALCAT1), that catalyzes pathological remodeling, biogenesis. We show overexpression ALCAT1 depletion mitofusin 2 (MFN2) expression. Strikingly, also leads to mtDNA instability are reminiscent MFN2 deficiency. Accordingly, expression completely rescues fusion defect respiratory dysfunction. Furthermore, ablation prevents from up-regulating expression, copy number, fidelity. Together, these findings reveal an unexpected remodeling biogenesis, linking defect.