Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in
maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups
between acetyl-CoA and carnitine. Show more
Carnitine O-acetyltransferase (CRAT) is a key mitochondrial enzyme involved in
maintaining metabolic homeostasis by mediating the reversible transfer of acetyl groups
between acetyl-CoA and carnitine. This enzymatic activity ensures the optimal functioning
of mitochondrial carbon flux by preventing acetyl-CoA accumulation, buffering metabolic
flexibility, and regulating the balance between fatty acid and glucose oxidation. CRAT’s interplay with the mitochondrial carnitine shuttle, involving carnitine palmitoyltransferases
(CPT1 and CPT2) and the carnitine carrier (SLC25A20), underscores its critical role in
energy metabolism. Emerging evidence highlights the structural and functional diversity of
CRAT and structurally related acetyltransferases across cellular compartments, illustrating
their coordinated role in lipid metabolism, amino acid catabolism, and mitochondrial
bioenergetics. Moreover, the structural insights into CRAT have paved the way for understanding its regulation and identifying potential modulators with therapeutic applications
for diseases such as diabetes, mitochondrial disorders, and cancer. This review examines
CRAT’s structural and functional aspects, its relationships with carnitine shuttle members
and other carnitine acyltransferases, and its broader role in metabolic health and disease.
The potential for targeting CRAT and its associated pathways offers promising avenues
for therapeutic interventions aimed at restoring metabolic equilibrium and addressing
metabolic dysfunction in disease states.
Luca, D.I.; Guerra, L.; Pierri, C.L.; De
Grassi, A. Carnitine
O-Acetyltransferase as a Central
Player in Lipid and Branched-Chain
Amino Acid Metabolism, Epigenetics, Show less