Mitochondrial diseases and ATPase defects of nuclear origin.
Dysfunctions of the F(1)F(o)-ATPase complex cause severe mitochondrial diseases affecting primarily the paediatric population. While in the maternally inherited ATPase defects due to mtDNA mutations in the ATP6 gene the enzyme is structurally and functionally modified, in ATPase defects of nuclear origin mitochondria contain a decreased amount of otherwise normal enzyme. In this case biosynthesis of ATPase is down-regulated due to a block at the early stage of enzyme assembly-formation of the F(1) catalytic part. The pathogenetic mechanism implicates dysfunction of Atp12 or other F(1)-specific assembly factors. For cellular energetics, however, the negative consequences may be quite similar irrespective of whether the ATPase dysfunction is of mitochondrial or nuclear origin.
Houstek
Josef
J
Institute of Physiology and Centre for Integrated Genomics, Academy of Sciences of the Czech Republic, Vídenská 1083, CZ 142 20 Prague 4-Krc, Czech Republic. houstek@biomed.cas.cz
Mrácek
Tomás
T
Vojtísková
Alena
A
Zeman
Jirí
J
D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D028361:Mitochondrial Diseases / Q000201:enzymology / Q000235:genetics*; D025261:Mitochondrial Proton-Translocating ATPases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D009154:Mutation; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism
D004272:DNA, Mitochondrial; C501005:MT-ATP6 protein, human; D017382:Reactive Oxygen Species; D000251:Adenosine Triphosphatases; D025262:Vacuolar Proton-Translocating ATPases; D025261:Mitochondrial Proton-Translocating ATPases