Succinate--CoA ligase [ADP/GDP-forming] subunit alpha, mitochondrial

SUCLG1 encodes the alpha subunit of succinate–CoA ligase, a mitochondrial enzyme catalyzing substrate-level phosphorylation in the citric acid cycle by coupling succinyl-CoA hydrolysis to ATP or GTP synthesis (UniProt: P53597). The protein also exhibits itaconyl- and malyl-CoA synthetase activity. The alpha subunit is responsible for binding coenzyme A and phosphate substrates, while regulatory specificity derives from associated beta subunits.

SUCLG1 is expressed in mitochondria and plays a central role in energy metabolism via the TCA cycle. Genetic variants in SUCLG1 cause mitochondrial DNA depletion syndrome 9 (MTDPS9), a severe infantile-onset disorder characterized by hypotonia, lactic acidosis, psychomotor retardation, and progressive neurologic deterioration (UniProt: P53597).

SUCLG1 is upregulated in Alzheimer's disease brain. Analysis of post-mortem AD tissue versus age-matched controls by TMT-labeled proteomics across four subcellular fractions revealed a mean log2 fold-change of +0.19 (Chaparral AD proteomics). This modest upregulation may reflect compensatory metabolic responses or altered mitochondrial function in AD pathology, though the functional consequence remains to be elucidated.