Mitogenomics: Recognizing the Significance of Mitochondrial Genomic Variation for Personalized Medicine

Inigo      Martinez-Romero; Sonia      Emperador; Laura      LLobet; Julio      Montoya; Eduardo      Ruiz-Pesini

Abstract

Over evolutionary time, human mitochondrial DNA (mtDNA) has accumulated many mutations. Because mtDNA is exclusively inherited from the maternal lineage, these mtDNA mutations have given rise to different mtDNA genetic backgrounds, or haplogroups. Human mtDNA codes subunits of the oxidative phosphorylation system and the RNAs required for the expression of these subunits. As this cell pathway is significant in cell homeostasis, mtDNA population polymorphisms may affect cell function, tissue dynamics and, finally, the health status of individuals. Supporting this idea, transmitochondrial cell lines differ in cellular, biochemical and molecular-genetic properties among mtDNA haplogroups. Moreover, several epidemiological studies suggest that population genetic variation in mtDNA can have important phenotypic effects and modify the predisposition of human beings toward different disorders. Human mitogenomics, the study of mtDNAs in humans, will allow the development of mtDNA barcodes connecting particular mtDNA haplotypes with higher/lower propensity to particular diseases. Importantly, mitogenomics offers a previously neglected avenue for the development of drugs to treat individuals according their mtDNA genetic background, raising the possibility of mitochondrially-personalized medicine.

Keywords: Haplogroup, mitogenomics, MtDNA, OXPHOS, personalized medicine, Mitochondrial Genomic Variation, mutation, homeostasis, OXIDATIVE PHOSPHORYLATION, PHENOTYPIC EFFECTS