# SUCLG2

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**Succinyl-CoA ligase [GDP-forming] subunit beta, mitochondrial** is an [enzyme](/source/Enzyme) that in humans is encoded by the *SUCLG2* [gene](/source/Gene) on chromosome 3.[1]

This gene encodes a [GTP](/source/Guanosine_triphosphate)-specific beta subunit of [succinyl-CoA synthetase](/source/Succinyl-CoA_synthetase). Succinyl-CoA synthetase [catalyzes](/source/Catalyze) the reversible reaction involving the formation of [succinyl-CoA](/source/Succinyl-CoA) and [succinate](/source/Succinate). [Alternate splicing](/source/Alternate_splicing) results in multiple transcript variants. [Pseudogenes](/source/Pseudogenes) of this gene are found on chromosomes 5 and 12. [provided by RefSeq, Apr 2010][1]

## Structure

SCS, also known as succinyl CoA ligase (SUCL), is a heterodimer composed of a catalytic α subunit encoded by the *[SUCLG1](/source/SUCLG1)* gene and a β subunit encoded by either the *[SUCLA2](/source/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.[2][3][4] [Amino acid](/source/Amino_acid) sequence alignment of the two β subunit types reveals a homology of ~50% identity, with specific regions conserved throughout the sequences.[5]

*SUCLG2* is located on chromosome 3 and contains 14 [exons](/source/Exon).[1]

## 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](/source/Acetoacetyl_CoA), accompanied by the [substrate-level phosphorylation](/source/Substrate-level_phosphorylation) of GDP to GTP, as a step in the tricarboxylic acid (TCA) cycle.[2][3][4][6] The GTP generated is then consumed in [anabolic](/source/Anabolism) pathways.[3][5] However, since GTP is not transported through the [inner mitochondrial membrane](/source/Inner_mitochondrial_membrane) in mammals and other higher organisms, it must be recycled within the matrix.[4] In addition, SUCLG2 may function in ATP generation in the absence of SUCLA2 by complexing with the mitochondrial nucleotide diphosphate [kinase](/source/Kinase), nm23-H4, and thus compensate for SUCLA2 deficiency.[2][4] The reverse reaction generates succinyl-CoA from succinate to fuel [ketone body](/source/Ketone_body) and [heme](/source/Heme) synthesis.[2][4]

While SCS is ubiquitously expressed, SUCLG2 is predominantly expressed in tissues involved in biosynthesis, including [liver](/source/Liver) and [kidney](/source/Kidney).[4][5][7] SUCLG2 has also been detected in the micro[vasculature](/source/Vasculature) of the brain, likely to support its growth.[3] Notably, both SUCLA2 and SUCLG2 are absent in [astrocytes](/source/Astrocyte), [microglia](/source/Microglia), and [oligodendrocytes](/source/Oligodendrocyte) in the [brain](/source/Brain); thus, in order to acquire succinate to continue the TCA cycle, these cells may instead synthesize succinate through [GABA](/source/GABA) metabolism of [α-ketoglutarate](/source/%CE%91-ketoglutarate) or ketone body metabolism of succinyl-CoA.[3][4]

## Clinical significance

Though [mitochondrial DNA (mtDNA) depletion syndrome](/source/Mitochondrial_DNA_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](/source/Oxidative_phosphorylation)-dependent growth.[2]

SUCLG2 may also play a role in clearing [cerebrospinal fluid](/source/Cerebrospinal_fluid) [amyloid-beta](/source/Amyloid-beta) 1–42 (Aβ1–42) in [Alzheimer's disease](/source/Alzheimer's_disease) (AD) and, thus, reducing neuronal death.[6]

## See also

- [Succinyl-CoA synthetase](/source/Succinyl-CoA_synthetase)
- [SUCLG1](/source/SUCLG1)
- [SUCLA2](/source/SUCLA2)

## References

1. ["Entrez Gene: SUCLA2 succinate-CoA ligase, GDP-forming, beta subunit"](https://www.ncbi.nlm.nih.gov/gene/8801)

1. Miller C, Wang L, Ostergaard E, Dan P, Saada A (May 2011). ["The interplay between SUCLA2, SUCLG2, and mitochondrial DNA depletion"](https://hal.archives-ouvertes.fr/hal-00679587/file/PEER_stage2_10.1016%252Fj.bbadis.2011.01.013.pdf). *Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease*. **1812** (5): 625–9. [doi:10.1016/j.bbadis.2011.01.013](https://doi.org/10.1016/j.bbadis.2011.01.013). [PMID 21295139](https://pubmed.ncbi.nlm.nih.gov/21295139)

1. Dobolyi A, Bagó AG, Gál A, Molnár MJ, Palkovits M, Adam-Vizi V, Chinopoulos C (April 2015). ["Localization of SUCLA2 and SUCLG2 subunits of succinyl CoA ligase within the cerebral cortex suggests the absence of matrix substrate-level phosphorylation in glial cells of the human brain"](http://real.mtak.hu/21651/1/Localization_CC.pdf). *Journal of Bioenergetics and Biomembranes*. **47** (1–2): 33–41. [doi:10.1007/s10863-014-9586-4](https://doi.org/10.1007/s10863-014-9586-4). [PMID 25370487](https://pubmed.ncbi.nlm.nih.gov/25370487). [S2CID 41101828](https://api.semanticscholar.org/CorpusID:41101828)

1. Dobolyi A, Ostergaard E, Bagó AG, Dóczi T, Palkovits M, Gál A, Molnár MJ, Adam-Vizi V, Chinopoulos C (January 2015). ["Exclusive neuronal expression of SUCLA2 in the human brain"](http://real.mtak.hu/17058/1/Bolyaihoz-Dobolyi-2014-BSF-humanSUCLA2.pdf). *Brain Structure & Function*. **220** (1): 135–51. [doi:10.1007/s00429-013-0643-2](https://doi.org/10.1007/s00429-013-0643-2). [PMID 24085565](https://pubmed.ncbi.nlm.nih.gov/24085565). [S2CID 105582](https://api.semanticscholar.org/CorpusID:105582)

1. Johnson JD, Mehus JG, Tews K, Milavetz BI, Lambeth DO (October 1998). "Genetic evidence for the expression of ATP- and GTP-specific succinyl-CoA synthetases in multicellular eucaryotes". *The Journal of Biological Chemistry*. **273** (42): 27580–6. [doi:10.1074/jbc.273.42.27580](https://doi.org/10.1074/jbc.273.42.27580). [PMID 9765291](https://pubmed.ncbi.nlm.nih.gov/9765291)

1. Ramirez A, van der Flier WM, Herold C, Ramonet D, Heilmann S, Lewczuk P, Popp J, Lacour A, Drichel D, Louwersheimer E, Kummer MP, Cruchaga C, Hoffmann P, Teunissen C, Holstege H, Kornhuber J, Peters O, Naj AC, Chouraki V, Bellenguez C, Gerrish A, Heun R, Frölich L, Hüll M, Buscemi L, Herms S, Kölsch H, Scheltens P, Breteler MM, Rüther E, Wiltfang J, Goate A, Jessen F, Maier W, Heneka MT, Becker T, Nöthen MM (December 2014). "SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease". *Human Molecular Genetics*. **23** (24): 6644–58. [doi:10.1093/hmg/ddu372](https://doi.org/10.1093/hmg/ddu372). [PMC 4240204](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240204). [PMID 25027320](https://pubmed.ncbi.nlm.nih.gov/25027320)

1. Matilainen S, Isohanni P, Euro L, Lönnqvist T, Pihko H, Kivelä T, Knuutila S, Suomalainen A (March 2015). "Mitochondrial encephalomyopathy and retinoblastoma explained by compound heterozygosity of SUCLA2 point mutation and 13q14 deletion". *European Journal of Human Genetics*. **23** (3): 325–30. [doi:10.1038/ejhg.2014.128](https://doi.org/10.1038/ejhg.2014.128). [PMC 4326715](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326715). [PMID 24986829](https://pubmed.ncbi.nlm.nih.gov/24986829)

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Adapted from the Wikipedia article [SUCLG2](https://en.wikipedia.org/wiki/SUCLG2) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/SUCLG2?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.