Assembly factors as a new class of disease genes for mitochondrial complex I deficiency: cause, pathology and treatment options.
Complex I deficiency is the most frequent cause of oxidative phosphorylation disorders. The disease features a large diversity of clinical symptoms often leading to progressive encephalomyopathies with a fatal outcome. There is currently no cure, and although disease-causing mutations have been found in the genes encoding complex I subunits, half of the cases remain unexplained. However, in the past 5 years a new class of complex I disease genes has emerged with the finding of specific assembly factors. So far nine such genes have been described and it is believed that in the near future more will be found. In this review, we will address whether the functions of these chaperones point towards a general molecular mechanism of disease and whether this enables us to design a treatment for complex I deficiency.
Nijmegen Centre for Mitochondrial Disorders at the Department of Paediatrics, Radboud University Nijmegen Medical Centre, 6500 HB, Nijmegen, The Netherlands.
Jessica
J
Nouws
Leo G J
LG
Nijtmans
Jan A
JA
Smeitink
Rutger O
RO
Vogel
D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000172:deficiency / Q000235:genetics; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000628:therapy; D018832:Molecular Chaperones / Q000235:genetics*; D010085:Oxidative Phosphorylation
D004272:DNA, Mitochondrial; D018832:Molecular Chaperones; D042967:Electron Transport Complex I