ALCAT1

ALCAT1 (acyl-CoA:lysocardiolipin acyltransferase 1) is an endoplasmic reticulum-associated acyltransferase that catalyzes cardiolipin remodeling through reacylation of monolysocardiolipin, thereby influencing mitochondrial membrane composition and bioenergetic function^[1][2]. Pathological activation of ALCAT1 promotes incorporation of polyunsaturated fatty acids into cardiolipin, increasing susceptibility to reactive oxygen species-mediated oxidation and driving a feed-forward cycle of cardiolipin depletion, oxidative stress, and mitochondrial dysfunction^[2][1][3]. Mechanistically, ALCAT1-dependent cardiolipin remodeling has been linked to mitochondrial fragmentation, reduced mitofusin 2 (MFN2) expression, impaired mitochondrial quality control, and altered mitophagy pathways in cellular and animal models^[1][4]. In disease models, elevated ALCAT1 activity contributes to metabolic, cardiovascular, neurodegenerative, and renal pathologies characterized by mitochondrial injury, including obesity, Parkinson’s disease, coronary artery disease, and diabetic kidney disease^[3][4][5]. Compared with related cardiolipin-remodeling enzymes such as tafazzin and mitochondrial monolysocardiolipin acyltransferase (MLCLAT1), ALCAT1 preferentially drives aberrant cardiolipin remodeling associated with oxidative stress rather than maintenance of physiological tetralinoleoyl cardiolipin composition^[2][1]. Therefore, genetic silencing or pharmacological inhibition of ALCAT1 has been widely applied to experimental studies investigating mitochondrial dysfunction, cardiolipin oxidation, and stress-induced tissue injury, supporting its utility as a mechanistic target in mitochondrial disease research^[3][4][5].