Mitochondrial respiratory chain disorders I: mitochondrial DNA defects

Mitochondria have a pivotal role in cell metabolism, being the major site o f ATP production via oxidative phosphorylation (OXPHOS); they have a critic al role in apoptotic cell death; and they also contribute to human genetics since mitochondria have a functional genome separate from that of nuclear DNA. Defects of mitochondrial metabolism are associated with a wide spectru m of disease. An important part of this spectrum is caused by mutations of mitochondrial DNA (mtDNA). These class I OXPHOS diseases are covered in par t I of this two-part review. Dysfunction of mitochondrial OXPHOS has also e merged as an important component of a range of predominantly neurodegenerat ive diseases in which the mitochondrial abnormality is most probably second ary. These class Il OXPHOS diseases are due to mutations of genes not encod ing OXPHOS subunits or are caused by exogenous or endogenous OXPHOS toxins. Class II mitochondrial diseases and the mitochondrion's role in apoptosis are covered in part II.