What happens when the mitochondrial permeability transition pore opens in response to cellular stress?

• A. The mitochondrial membrane potential is maintained and ATP synthesis proceeds normally.
• B. Cytosolic calcium levels increase.
• C. The mitochondrial membrane potential collapses and cytochrome c is released, activating caspases.
• D. Reactive oxygen species are completely eliminated.

Answer: (C)

Opening the mitochondrial permeability transition pore creates a large, non-selective channel in the inner mitochondrial membrane. This dissipates the proton motive force, so the mitochondrial membrane potential collapses and ATP production by oxidative phosphorylation halts. The resulting osmotic imbalance causes the mitochondrial matrix to swell, and the outer membrane can rupture, releasing cytochrome c into the cytosol. Once cytochrome c is in the cytosol, it helps assemble the apoptosome with Apaf-1 and procaspase-9, activating caspases and steering the cell toward apoptosis. This sequence explains why the membrane potential collapse and cytochrome c release are the defining consequences of pore opening under cellular stress.