SUCLG2

SCS, also known as succinyl CoA ligase (SUCL), is a heterodimer composed of a catalytic α subunit encoded by the SUCLG1 gene and a β subunit encoded by either the SUCLA2 gene or the SUCLG2 gene, which determines the enzyme specificity for either ADP or GDP. SUCLG2 is the SCS variant containing the SUCLG2-encoded β subunit. Amino acid sequence alignment of the two β subunit types reveals a homology of ~50% identity, with specific regions conserved throughout the sequences. SUCLG2 is located on chromosome 3 and contains 14 exons. == Function ==

As a subunit of SCS, SUCLG2 is a mitochondrial matrix enzyme that catalyzes the reversible conversion of succinyl-CoA to succinate and acetoacetyl CoA, accompanied by the substrate-level phosphorylation of GDP to GTP, as a step in the tricarboxylic acid (TCA) cycle. The GTP generated is then consumed in anabolic pathways. SUCLG2 has also been detected in the microvasculature of the brain, likely to support its growth. Notably, both SUCLA2 and SUCLG2 are absent in astrocytes, microglia, and oligodendrocytes in the brain; thus, in order to acquire succinate to continue the TCA cycle, these cells may instead synthesize succinate through GABA metabolism of α-ketoglutarate or ketone body metabolism of succinyl-CoA. == Clinical significance ==

Though mitochondrial DNA (mtDNA) depletion syndrome has been largely attributed to SUCLA2 deficiency, SUCLG2 may play a more crucial role in mtDNA maintenance, as it functions to compensate for SUCLA2 deficiency and its absence results in decreased mtDNA and OXPHOS-dependent growth. SUCLG2 may also play a role in clearing cerebrospinal fluid amyloid-beta 1–42 (Aβ1–42) in Alzheimer's disease (AD) and, thus, reducing neuronal death. == See also ==