SUCLG1 explained

Succinyl-CoA ligase [GDP-forming] subunit alpha, mitochondrial is an enzyme that in humans is encoded by the SUCLG1 gene.^{[1] [2]}

Structure

The enzyme encoded by SUCLG1 can exist in either a phosphorylated form or a dephosphorylated form. In the dephosphorylated structure, a phosphate ion works in coordination with a histidine residue in the active site and the two alpha helices, one contributed by each subunit of the alphabeta-dimer to stabilize the structure. One of the alpha helices contains amino acids, the modification of which result in conformational changes that accommodate either the bound phosphoryl group or the free phosphate ion.^[3]

Function

This gene encodes the alpha subunit of the heterodimeric enzyme succinate coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of succinyl CoA and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile lactic acidosis and mitochondrial DNA depletion.^{[4] [5]}

Clinical significance

Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLG1 lead to complete absence of SUCLG1 protein and are responsible for a very severe disorder with antenatal manifestations. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in fibroblasts by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent.^[6] As mitochondrial DNA depletion in muscle is not a constant finding in SUCLG1 patients, diagnosis should not be based on it; additionally, it may be that alternative physiopathological mechanisms may be considered to explain the combined respiratory chain deficiency observed in these patients.^[5]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . Oct 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Fraser ME, James MN, Bridger WA, Wolodko WT . Phosphorylated and dephosphorylated structures of pig heart, GTP-specific succinyl-CoA synthetase . Journal of Molecular Biology . 299 . 5 . 1325–39 . Jun 2000 . 10873456 . 10.1006/jmbi.2000.3807 .
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions . Genome Research . 14 . 9 . 1711–8 . Sep 2004 . 15342556 . 515316 . 10.1101/gr.2435604 .
• Tsang HT, Connell JW, Brown SE, Thompson A, Reid E, Sanderson CM . A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex . Genomics . 88 . 3 . 333–46 . Sep 2006 . 16730941 . 10.1016/j.ygeno.2006.04.003 . free .
• Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F . Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion . American Journal of Human Genetics . 81 . 2 . 383–7 . Aug 2007 . 17668387 . 1950792 . 10.1086/519222 .

Notes and References

1. James M, Man NT, Edwards YH, Morris GE . The molecular basis for cross-reaction of an anti-dystrophin antibody with alpha-actinin . Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease . 1360 . 2 . 169–76 . Apr 1997 . 9128182 . 10.1016/s0925-4439(96)00076-2 . free .
2. Web site: Entrez Gene: SUCLG1 succinate-CoA ligase, GDP-forming, alpha subunit.
3. Fraser ME, James MN, Bridger WA, Wolodko WT . Phosphorylated and dephosphorylated structures of pig heart, GTP-specific succinyl-CoA synthetase . Journal of Molecular Biology . 299 . 5 . 1325–39 . Jun 2000 . 10873456 . 10.1006/jmbi.2000.3807 .
4. Ostergaard E . Disorders caused by deficiency of succinate-CoA ligase . Journal of Inherited Metabolic Disease . 31 . 2 . 226–9 . Apr 2008 . 18392745 . 10.1007/s10545-008-0828-7 . 12722653 .
5. Valayannopoulos V, Haudry C, Serre V, Barth M, Boddaert N, Arnoux JB, Cormier-Daire V, Rio M, Rabier D, Vassault A, Munnich A, Bonnefont JP, de Lonlay P, Rötig A, Lebre AS . New SUCLG1 patients expanding the phenotypic spectrum of this rare cause of mild methylmalonic aciduria . Mitochondrion . 10 . 4 . 335–41 . Jun 2010 . 20197121 . 10.1016/j.mito.2010.02.006 .
6. Rouzier C, Le Guédard-Méreuze S, Fragaki K, Serre V, Miro J, Tuffery-Giraud S, Chaussenot A, Bannwarth S, Caruba C, Ostergaard E, Pellissier JF, Richelme C, Espil C, Chabrol B, Paquis-Flucklinger V . The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein . Journal of Medical Genetics . 47 . 10 . 670–6 . Oct 2010 . 20693550 . 10.1136/jmg.2009.073445 . 35860287 .