title: Forty years later: Mitochondria as therapeutic targets in muscle diseases.
abstract: The hypothesis that mitochondrial dysfunction can be a general mechanism for cell death in muscle diseases is 40 years old. The key elements of the proposed pathogenetic sequence (cytosolic Ca2+overload followed by excess mitochondrial Ca2+uptake, functional and then structural damage of mitochondria, energy shortage, worsened elevation of cytosolic Ca2+levels, hypercontracture of muscle fibers, cell necrosis) have been confirmed in amazing detail by subsequent work in a variety of models. The explicit implication of the hypothesis was that it "may provide the basis for a more rational treatment for some conditions even before their primary causes are known" (Wrogemann and Pena, 1976, Lancet, 1, 672-674). This prediction is being fulfilled, and the potential of mitochondria as pharmacological targets in muscle diseases may soon become a reality, particularly through inhibition of the mitochondrial permeability transition pore and its regulator cyclophilin D.
authors.affiliation: CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zulian
authors.affiliation: CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Schiavone
authors.affiliation: CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Giorgio
authors.affiliation: CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy. Electronic address: bernardi@bio.unipd.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D009135:Muscular Diseases / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D021983:Cyclophilins; D002118:Calcium
keywords: Calcium; Cyclophilins; Mitochondria; Muscle diseases; Permeability transition; Therapy