Acute tobacco smoke exposure promotes mitochondrial permeability transition in rat heart

Chronic exposure to tobacco smoke is known to impair mitochondrial function. However, the effect of acute tobacco smoke exposure (ATSE) in vivo, as might occur in social settings, on mitochondrial function and calcium handling of cardiac cells has not been examined. It was hypothesized that ATSE might adversely modify mitochondrial function as reflected in mitochondrial energetics, membrane potential, and calcium transport. Mitochondria were isolated from the hearts of adult rats either exposed to 6 h of environmental tobacco smoke (∼60 mg/mm 3 tobacco smoke particles) or sham exposure. To model a calcium stress similar to ischemia/reperfusion, mitochondria were exposed to a Ca 2+ bolus with measurement of membrane potential, energetics, Ca 2+ uptake and release, and redox state. ATSE mitochondria were characterized by significantly higher ADP-stimulated ATP production and a more reduced redox state (NADH ratio) under basal conditions without observed changes in resting Ψ m. Exposure of ATSE mitochondria to Ca 2+ stress resulted in significantly more rapid depolarization of Ψ m. The initial rate of Ca 2+ uptake was not altered in ATSE mitochondria, but CsA-sensitive Ca 2+ release was significantly increased. ATSE does not significantly alter resting mitochondrial function. However, ATSE modifies the response of cardiac mitochondria to calcium stress, resulting in a more rapid depolarization and subsequent release of Ca 2+ via the mitochondrial permeability transition (MPT). Copyright