Succinyl-CoA ligase ADP-forming subunit beta (SUCLA2)

Succinyl-CoA ligase ADP-forming subunit beta (SUCLA2) is the ATP-specific beta subunit of succinyl-CoA synthetase, a mitochondrial matrix enzyme essential for substrate-level phosphorylation in the tricarboxylic acid cycle[1][3][8]. When combined with the alpha subunit (SUCLG1), SUCLA2 forms SCS-A, catalyzing the reversible conversion of succinyl-CoA and ADP to succinate and ATP, a reaction vital for cellular energy production, especially in energy-demanding tissues such as brain and muscle[1][2][5]. SUCLA2 also interacts with nucleoside diphosphate kinase to help maintain mitochondrial DNA integrity[3][9]. Pathogenic variants cause mitochondrial DNA depletion syndrome and Leigh syndrome, with profound impacts on neuromuscular development and survival[6][9]. In cancer, SUCLA2 supports metastatic cell survival by regulating redox balance through a noncanonical mechanism involving stress granule formation and antioxidant enzyme translation[7]. The enzyme is thus a potential therapeutic target in oncology and mitochondrial medicine, though direct drugs have yet to be clinically approved[7].

Other names

SUCLA2SCS-betaAA-SCSMTDPS5A-BETAsuccinate-CoA ligase ADP-forming beta subunitsuccinate-CoA ligase ADP-forming subunit betaLINC00444succinyl-CoA synthetase ATP-specific subunit beta

Enzyme inhibition leading to impaired ATP generation. Disruption of stress granule formation and antioxidant enzyme expression (experimental anticancer approaches). Modulation of mitochondrial metabolic activity.