Analysis of oxygen consumption and mitochondrial permeability with age in mice.
Biochemical and physiological parameters have been investigated in purified liver mitochondria from C57BL/6J mice of relatively young and old age, 1 month vs. 36 months. Under identical purification conditions, mitochondria from old animals consumed significantly less O2 under state 3 conditions (i.e. with saturating ADP stimulation), consistent with a lower activity of the electron transport chain. In the absence of ADP (i.e. state 4 conditions), old mitochondria consumed significantly more O2 than young mitochondria; one possible explanation was increased mitochondrial permeability as a result of induction of the mitochondrial permeability transition (MPT), and this was investigated by the mitochondrial swelling assay. In response to induction by 20 microM Ca2+, MPT rates were observed to be variable, but significantly faster in old mitochondria (t1/2 = 105 s) than in young mitochondria (t1/2 = 155 s), and in all cases MPT was inhibitable by cyclosporin A (CsA). The implications of lower state 3 respiration, higher state 4 respiration and increased rate of MPT in old mitochondria are discussed.
Goodell
S
S
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
Cortopassi
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G
D000375:Aging / Q000502:physiology*; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000378:metabolism / Q000502:physiology*; D008933:Mitochondrial Swelling / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology*; D019802:Succinic Acid / Q000378:metabolism
D019802:Succinic Acid