title: Mitochondrial genome changes and neurodegenerative diseases.
abstract: Mitochondria are essential organelles within the cell where most of the energy production occurs by the oxidative phosphorylation system (OXPHOS). Critical components of the OXPHOS are encoded by the mitochondrial DNA (mtDNA) and therefore, mutations involving this genome can be deleterious to the cell. Post-mitotic tissues, such as muscle and brain, are most sensitive to mtDNA changes, due to their high energy requirements and non-proliferative status. It has been proposed that mtDNA biological features and location make it vulnerable to mutations, which accumulate over time. However, although the role of mtDNA damage has been conclusively connected to neuronal impairment in mitochondrial diseases, its role in age-related neurodegenerative diseases remains speculative. Here we review the pathophysiology of mtDNA mutations leading to neurodegeneration and discuss the insights obtained by studying mouse models of mtDNA dysfunction.
authors.affiliation: Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Milena
authors.initials: M
authors.lastname: Pinto
authors.affiliation: Department of Neurology, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Neuroscience Graduate Program, University of Miami Miller School of Medicine, Miami, FL 33136, USA; Department of Cell Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. Electronic address: cmoraes@med.miami.edu.
authors.forename: Carlos T
authors.initials: CT
authors.lastname: Moraes
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D004195:Disease Models, Animal; D054629:Genome, Mitochondrial / Q000235:genetics*; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial
keywords: Encephalopathy; Mitochondrion; mtDNA