Using single-cell analysis, Waterhouse et al. (page 319) tracked changes in the mitochondrial transmembrane potential after apoptotic cytochrome c release and found that, in the absence of caspase activity, permeabilized mitochondria can regenerate their membrane potential sufficiently to generate ATP. The findings help resolve an apparent paradox in apoptosis: ATP is required for programmed cell death, but the release of cytochrome c through the mitochondrial outer membrane could potentially interfere with ATP generation via oxidative phosphorylation.
In the new work, cells were triggered to undergo apoptosis in the presence of caspase inhibitors, causing the release of cytochrome c from mitochondria but preventing downstream apoptotic events. In this system, the mitochondrial transmembrane potential rapidly depolarizes, but recovers to its original levels within 60 min, after which it is maintained at levels sufficient to generate ATP using cytoplasmic cytochrome c. The...
