Nuclear genes, mutations mitochondrial diseases

A mutation in any of the 13 protein subunits, the 22 tRNAs, or the two rRNAs whose genes are carried in mitochondrial DNA may possibly cause disease. The 13 protein subunits are all involved in electron transport or oxidative phosphorylation. The syndromes resulting from mutations in mtDNA frequently affect oxidative phosphorylation (OXPHOS) causing what are often called "OXPHOS diseases."3-6 Mitochondrial oxidative phosphorylation also depends upon 100 proteins encoded in the nucleus. Therefore, OXPHOS diseases may result from defects in either mitochondrial or nuclear genes. The former are distinguished by the fact that they are inherited almost exclusively maternally. Most mitochondrial diseases are rare. However, mtDNA is subject to rapid mutation, and it is possible that accumulating mutants in mtDNA may be an important component of aging.h k... 

Defects of nuclear DNA also cause mitochondrial diseases. As mentioned above, the vast majority of mitochondrial proteins are encoded by nDNA, synthesized in the cytoplasm and imported into the mitochondria through a complex series of steps. Diseases can be due to mutations in genes encoding respiratory chain subunits, ancillary proteins controlling the proper assembly of the respiratory chain complexes, proteins controlling the importation machinery, or proteins controlling the lipid composition of the inner membrane. All these disorders will be transmitted by mendelian inheritance. From a biochemical point of view, all areas of mitochondrial metabolism can be affected (see below). 

Mutations in Nuclear Genes and Animal Models of Mitochondrial Diseases... 106... 

In 1995, Bourgeron et al. (B7) first reported that mutation in a nuclear gene coding for succinate dehydrogenase may result in mitochondrial disease. In 1998,... 

Mutations in the genes that encode components of the respiratory chain, whether in the mitochondrial genes or in the nuclear genes that encode mitochondrial proteins, cause a variety of human diseases, which often affect muscle and brain most severely. 

Clinical diseases involving components of oxidative phosphorylation (referred to as OXPHOS diseases) are among the most commonly encountered degenerative diseases. The clinical pathology may be caused by gene mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) that encode proteins required for normal oxidative phosphorylation. 

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