Deficiency of the ADP-forming succinyl-CoA synthase activity is associated with encephalomyopathy and mitochondrial DNA depletion.
The mitochondrial DNA (mtDNA) depletion syndrome is a quantitative defect of mtDNA resulting from dysfunction of one of several nuclear-encoded factors responsible for maintenance of mitochondrial deoxyribonucleoside triphosphate (dNTP) pools or replication of mtDNA. Markedly decreased succinyl-CoA synthetase activity due to a deleterious mutation in SUCLA2, the gene encoding the beta subunit of the ADP-forming succinyl-CoA synthetase ligase, was found in muscle mitochondria of patients with encephalomyopathy and mtDNA depletion. Succinyl-CoA synthetase is invariably in a complex with mitochondrial nucleotide diphosphate kinase; hence, we propose that a defect in the last step of mitochondrial dNTP salvage is a novel cause of the mtDNA depletion syndrome.
Elpeleg
Orly
O
Metabolic Disease Unit, Shaare-Zedek Medical Center, Jerusalem, Israel. Elpeleg@cc.huji.ac.il.
Miller
Chaya
C
Hershkovitz
Eli
E
Bitner-Glindzicz
Maria
M
Bondi-Rubinstein
Gili
G
Rahman
Shamima
S
Pagnamenta
Alistair
A
Eshhar
Sharon
S
Saada
Ann
A
D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D005091:Exons; D017353:Gene Deletion; D005819:Genetic Markers; D015894:Genome, Human; D006720:Homozygote; D006801:Humans; D007438:Introns; D018895:Microsatellite Repeats; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D017422:Sequence Analysis, DNA; D013389:Succinate-CoA Ligases / Q000172:deficiency*
D004272:DNA, Mitochondrial; D003854:Deoxyribonucleotides; D005819:Genetic Markers; D013389:Succinate-CoA Ligases