ACSS2 involved in acetyl-CoA synthesis regulates skeletal muscle function.

ABSTRACT: Acyl-coenzyme A synthetase short-chain family member-2 (ACSS2) catalyzes the conversion of acetate to acetyl-CoA, regulating cholesterol metabolism. Given the discovery of a muscular dystrophy associated with 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR), a key enzyme in cholesterol synthesis, we studied Acss2 in mice and the orthologous gene AcCoA in flies. Skeletal muscle from Acss2^-/- mice showed atrophic fibers, lipid accumulation, and depleted NADH levels, while myoblasts from these mice displayed precocious differentiation. Exercise induced fatigue in the Acss2^-/- mice, which was accentuated by inhibition of ATP-citrate lyase (ACLY) activity. AcCoA knockdown yielded reduced body sizes and locomotor defects in Drosophila. ACSS2 is vital for skeletal mu

SUBMITTER: Gunasekaran M 

PROVIDER: S-EPMC12519054 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature