Genetics of Mitochondrial Disease.
Mitochondria are intracellular organelles responsible for adenosine triphosphate production. The strict control of intracellular energy needs require proper mitochondrial functioning. The mitochondria are under dual controls of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Mitochondrial dysfunction can arise from changes in either mtDNA or nDNA genes regulating function. There are an estimated ∼1500 proteins in the mitoproteome, whereas the mtDNA genome has 37 proteins. There are, to date, ∼275 genes shown to give rise to disease. The unique physiology of mitochondrial functioning contributes to diverse gene expression. The onset and range of phenotypic expression of disease is diverse, with onset from neonatal to seventh decade of life. The range of dysfunction is heterogeneous, ranging from single organ to multisystem involvement. The complexity of disease expression has severely limited gene discovery. Combining phenotypes with improvements in gene sequencing strategies are improving the diagnosis process. This chapter focuses on the interplay of the unique physiology and gene discovery in the current knowledge of genetically derived mitochondrial disease.
['Saneto|Russell P|RP|']
D004261:DNA Replication D004272:DNA, Mitochondrial D015316:Genetic Therapy D006801:Humans D008928:Mitochondria D028361:Mitochondrial Diseases D009154:Mutation D010085:Oxidative Phosphorylation D010641:Phenotype
Mitochondrial disease Mitochondrial DNA Mitochondrial inheritance Nuclear-encoded mitochondrial disease Oxidative phosphorylation mtDNA replication mtDNA transcription mtDNA translation mtDNA-encoded disease