ATP at a Crossroads: Cell Life or Death?

In the good old days, the picture of the mitochondrial universe was simple. Good mitochondria produce ATP, which is then used for many cell functions as well as to synthesize the multi-thousands of types of macromolecules that are necessary for the cell to exist. These good old days of simple biology are long gone in the wake of new findings: the ATP level or the available energy has been identified as one of the key factors determining the cell death via apoptosis or necrosis. The finding that depletion of ATP during apoptosis prevents the execution of apoptosis, but converts the cell death pathways to necrosis, is consistent with the fact that the apoptotic program has energy-requiring steps, including: (i) apoptosome complex formation and processing of pro-caspase-9; (ii) chromatin condensation and apoptotic body formation; (iii) phosphorylation of kinases. Thus, in apoptosis the role of both ATP, mostly produced in the mitochondria by oxidative phosphorylation, and the mitochondrial adenine-nucleotide translocator, through which the ATP reaches the cytosol, is crucial.