Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial

SUCLA2 encodes the beta subunit of succinate–CoA ligase [ADP-forming], a mitochondrial enzyme catalyzing substrate-level phosphorylation in the citric acid cycle by coupling succinyl-CoA hydrolysis to ATP synthesis (UniProt: Q9P2R7). The beta subunit confers nucleotide specificity and binds succinate, while the enzyme also exhibits itaconyl- and malyl-CoA synthetase activity.

SUCLA2 mutations cause mitochondrial DNA depletion syndrome 5 (MTDPS5; MIM 612073), a severe disorder featuring infantile-onset hypotonia, neurologic deterioration, movement disorders, ophthalmoplegia, and hearing loss (UniProt: Q9P2R7). The protein's central role in TCA cycle energy metabolism links it to mitochondrial homeostasis across tissues.

SUCLA2 is downregulated in Alzheimer's disease brain tissue (mean log2FC −1.37, Chaparral AD proteomics). This reduction in a key TCA enzyme may reflect impaired mitochondrial oxidative metabolism, a hallmark of AD pathophysiology. The downregulation was detected across post-mortem AD brain subcellular fractions relative to age-matched controls, suggesting a broad metabolic compromise in diseased tissue.