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.