Nuclear genetic disorders of mitochondrial DNA gene expression

Abstract While the mitochondrial genome encodes 13 essential proteins required for mitochondrial oxidative phosphorylation, together with the RNA complement required for mitochondrial translation, the majority of mitochondrial proteins—and specifically those required for the posttranslational expression of all mitochondrial DNA-encoded genes—are encoded by the nuclear genome. Here, we outline the mechanisms through which mitochondrial DNA-encoded genes are expressed, reviewing the current knowledge of Mendelian mitochondrial disease genes and human disease clinical phenotypes associated with inherited defects of these processes.