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Defining the precise sequence of events that occur during apoptosis is an important but yet-to-be-realized goal of cell death research. For example, permeabilization of the mitochondrial outer membrane is known to lead to release of cytochrome c (cytC) from mitochondria, apoptosome formation and activation of effector caspases, but how and when cellular bioenergetics is affected is still debated. Jochen Prehn and co-workers have therefore analysed mitochondrial and plasma membrane depolarization during apoptosis of cells expressing GFP-cytC fusion proteins, using time-lapse confocal fluorescence microscopy (see p. 525). They find that following cytC release mitochondria rapidly depolarize but not completely. The organelles establish a new steady-state potential, which appears to be maintained by reversal of the FoF1-ATPase since it can be abolished by oligomycin. The authors observe that the initial mitochondrial depolarization is coupled to depolarization of the plasma membrane. Furthermore, they demonstrate that, unlike mitochondrial depolarization, the latter requires caspases and is associated with degradation of the plasma membrane Na+/K+-ATPase. The authors' findings thus illuminate not only the sequence of events in mitochondria but also how they influence what happens at the plasma membrane during cell death.
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