Individual Cardiac Mitochondria Undergo Rare Transient Permeability Transition Pore Openings

Mitochondria sustain cellular life through energy production but also mediate programmed cell death. ATP production is mainly via cellular respiration, which is driven by the voltage gradient (ΔΨ m ) across the inner mitochondrial membrane that drives proton flux through the F 0 F 1 –ATP synthase. Extremely low resting inner mitochondrial membrane permeability is critical to maintain high ΔΨ m and ATP synthesis rate in living cells. However, under certain stresses, the inner mitochondrial membrane undergoes a permeability transition pore opening (mPTP), abolishing ΔΨ m and allowing molecules of ≤1500 Da in size to freely permeate. This causes respiratory uncoupling, metabolite loss (eg, NADH), cessation of ATP synthesis, increased ATP consumption (via F 0 F 1 –ATP synthase), and mitochondrial and cell death.