Mitochondrial function and myocardial aging. A critical analysis of the role of permeability transition.
Mitochondria have been suggested to be causally linked to age-related alterations through respiratory chain dysfunction and formation of reactive oxygen species, leading to damage of mitochondrial DNA. Impaired biosynthesis of respiratory chain and ATP synthase subunits encoded by mitochondrial genes would set up a vicious cycle contributing to the aging process. Mitochondria are also involved in the increased susceptibility to ischemic injury observed in aged hearts, a process where the mitochondrial permeability transition pore (PTP) may play a role. Here, we analyze (i) the possible mechanisms through which PTP opening might contribute to age-related myocardial alterations; (ii) the available evidence of an increased probability of PTP opening in mitochondria isolated from aged tissues; (iii) the current methodological limitations that complicate the elucidation of causal relationships between PTP opening, mitochondrial dysfunction, and myocardial aging.
Di Lisa
Fabio
F
Dipartimento di Chimica Biologica, Università di Padova, Viale G. Colombo 3, 35121 Padova, Italy. dilisa@civ.bio.unipd.it
Bernardi
Paolo
P
D000375:Aging / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D019069:Cell Respiration; D004249:DNA Damage; D004272:DNA, Mitochondrial; D004579:Electron Transport; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008929:Mitochondria, Heart / Q000502:physiology*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D004272:DNA, Mitochondrial; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D017382:Reactive Oxygen Species; D000226:Mitochondrial ADP, ATP Translocases; D002118:Calcium