ACSS2 involved in acetyl‐CoA synthesis regulates skeletal muscle function

TL;DR

ACSS2 is essential for skeletal muscle function, as its deficiency causes muscle atrophy, lipid accumulation, and impaired movement in mice and flies.

Contribution

This study reveals ACSS2's role in skeletal muscle function and metabolism, linking it to cholesterol pathways and muscle diseases.

Findings

ACSS2 deficiency in mice causes muscle atrophy, lipid accumulation, and reduced NADH levels.

ACSS2 deficiency in flies leads to reduced body size and locomotor defects.

ACSS2 is crucial for maintaining skeletal muscle function and metabolism.

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 muscle function and merits study as a potential factor in muscle diseases related to cholesterol metabolism.

Impact statementACSS2 catalyzes the conversion of acetate to acetyl‐CoA, regulating cholesterol metabolism. Given the increasingly apparent links between cholesterol metabolism and skeletal muscle function, we investigated ACSS2 deficiency in mouse and fly models. We identified defects in muscle morphology, muscle metabolism, and motor function. ACSS2 is vital for skeletal muscle.

ACSS2 catalyzes the conversion of acetate to acetyl‐CoA, regulating cholesterol metabolism. Given the increasingly apparent links between cholesterol metabolism and skeletal muscle function, we investigated ACSS2 deficiency in mouse and fly models. We identified defects in muscle morphology, muscle metabolism, and motor function. ACSS2 is vital for skeletal muscle.

The enzyme acyl‐coenzyme A synthetase short‐chain family member‐2 (ACSS2) catalyzes the conversion of acetate to acetyl‐CoA, but its function in skeletal muscle is unclear. We studied ACSS2 deficiency in mouse and fly models. Skeletal muscle from the mouse model showed atrophic fibers, excess lipid, and depleted NADH. The fly model showed locomotor defects. ACSS2 is important for skeletal muscle function.

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