title: Pathogenesis and treatment of mitochondrial myopathies: recent advances.
abstract: In this brief review, I have highlighted recent advances in several areas of mitochondrial medicine, including mtDNA-related diseases, mendelian mitochondrial encephalomyopathies, and therapy. The pathogenic mechanisms of mtDNA mutations, especially those affecting mitochondrial protein synthesis, are still largely unknown. The pathogenicity of homoplasmic mtDNA mutations has become evident but has also called attention to modifying nuclear genes, yet another example of impaired intergenomic signaling. The functional significance of the homoplasmic changes associated with mitochondrial haplogroups has been confirmed. Among the mendelian disorders, a new form of "indirect hit" has been described, in which the ultimate pathogenesis is toxic damage to the respiratory chain. Three therapeutic strategies look promising: (i) allogeneic hematopoietic stem cell transplantation in MNGIE (mitochondrial neurogastrointestinal encephalomyopathy); (ii) bezafibrate, an activator of PGC-1alpha, has proven effective in animal models of mitochondrial myopathy; and (iii) pronucleus transfer into a normal oocyte is effective in eliminating maternal transmission of mtDNA, thus preventing the appearance of mtDNA-related disorders.
authors.affiliation: Department of Neurology, Columbia University Medical Center, College of Physicians & Surgeons, New York, NY 10032, USA. sd12@columbia.edu
authors.forename: S
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000818:Animals; D001629:Bezafibrate / Q000627:therapeutic use; D004272:DNA, Mitochondrial / Q000235:genetics; D004195:Disease Models, Animal; D018380:Hematopoietic Stem Cell Transplantation / Q000639:trends; D006801:Humans; D017240:Mitochondrial Myopathies / Q000209:etiology* / Q000628:therapy*; D009154:Mutation / Q000235:genetics; D053652:Nuclear Transfer Techniques / Q000639:trends
chemical_list: D004272:DNA, Mitochondrial; D001629:Bezafibrate