The significance of the ketolytic gene OXCT1 in metabolism, intracellular signaling and disease development

OXCT1 (3-oxoacid CoA-transferase 1), encoding the mitochondrial enzyme SCOT (succinyl-CoA:3-ketoacid CoA transferase), is a key enzyme in ketone body utilization. It catalyzes the reversible transfer of CoA from succinyl-CoA to acetoacetate, generating acetoacetyl-CoA, which is subsequently converted into acetyl-CoA for entry into the tricarboxylic acid (TCA) cycle and mitochondrial energy production. Although classically regarded as a metabolic enzyme, emerging evidence indicates that OXCT1 participates in broader regulatory networks. In addition to its protein-coding transcript, the OXCT1 locus produces regulatory non-coding RNAs, including circ-OXCT1 and lncRNA OXCT1-AS1, which provides additional levels of regulation, as for now reported in various types of cancer. Moreover, the review summarizes current knowledge on OXCT1 biochemical function, regulation, and tissue distribution, with emphasis on transcriptional control, post-translational modifications such as lysine succinylation and redox-dependent regulation, and integration with nutrient-sensing and stress-response pathways. By combining recent literature with bioinformatics analysis, we demonstrate that OXCT1 displays highly dynamic expression across diverse cancer types and metabolic states, consistent with a role in metabolic plasticity and disease progression. Furthermore, we discuss here the OXCT1 role in other pathological conditions including metabolic disorders, neurological disease, and cardiomyopathy, implicating both metabolic dysfunction and aberrant protein modification in disease mechanisms. Collectively, these findings establish OXCT1 as a central regulator of metabolic adaptation and a potential therapeutic target.