Mitochondrial complex I dysfunction in rat heart with aging: critical role of reactive oxygen species and cardiolipin.
Reactive oxygen species (ROS) are considered a key factor in the heart aging process. Mitochondrial respiration is an important site of ROS generation and a potential contributor to heart functional changes with aging. We have examined the effects of aging on various parameters related to mitochondrial bioenergetics in rat heart, such as complex I activity, oxygen consumption, membrane potential, ROS production, and cardiolipin content and oxidation. A loss in complex I activity, state 3 respiration, and membrane potential was found in mitochondria with aging. The capacity of mitochondria to produce H(2)O(2) was significantly increased in aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, significantly decreased as a function of aging, whereas there was a significant increase in the level of oxidized cardiolipin. The lower complex I activity in mitochondria from aged rats could be almost completely restored to the level of young heart by exogenously added cardiolipin, but not by other phospholipids nor by peroxidized cardiolipin. It is proposed that aging causes heart mitochondrial complex I deficiency, which can be attributed to ROS-induced cardiolipin peroxidation. These results may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with heart aging.
Petrosillo
Giuseppe
G
Department of Biochemistry and Molecular Biology, CNR Institute of Biomembranes and Bioenergetics, University of Bari, Italy.
Matera
Mariagiuseppa
M
Moro
Nicola
N
Ruggiero
Francesca M
FM
Paradies
Giuseppe
G
D000375:Aging / Q000502:physiology*; D000818:Animals; D002308:Cardiolipins / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002950:Citrate (si)-Synthase / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008929:Mitochondria, Heart / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012119:Respiration
D002308:Cardiolipins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I