Published 6 January 2003. doi:10.1083/jcb1601iti2
© The Rockefeller University Press,
0021-9525/2003/1/6-a $5.00
The Journal of Cell Biology, Volume 160, Number 1, 6-a-6
Caspases chew on electron transport
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Mitochondrial oxygen consumption in response to complex I and II substrates is reduced by caspase treatment (blue).
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Caspases seem to have their hand in everything during apoptosis. They cleave and activate enzymes that degrade DNA, induce cell blebbing, and induce changes in the plasma membrane that make the dying cell attractive to phagocytes. Now, add another to the list—caspases disturb electron transport.
Ricci et al. (page 65) show that, in both isolated mitochondria and living cells, caspase-3 induces a loss of membrane potential in mitochondria that have been permeabilized by proapoptotic proteins. Inhibition of caspase activity prevented this loss in potential, which places membrane potential loss downstream of cytochrome c release and subsequent activation of caspases.
Mitochondria lost membrane potential because complexes I and II were injured. Caspase-treated permeabilized mitochondria did not consume oxygen in response to substrates used by complexes I and II, although the other complexes remained intact. The interference of the transfer of electrons by complexes I and II to complex III produced reactive oxygen species and is expected to limit ATP production and disturb mitochondrial metabolism. Together, these effects may be critical for dismantling the cell during death, although their importance has not been established. The authors are currently identifying caspase substrates within complexes I and II. They will then determine whether blocking cleavage of these substrates changes either mitochondrial responses to caspases or the pattern of cell death.
Even with fully functioning complexes I and II, apoptosis may still induce DNA damage and cytoskeletal and plasma membrane changes that lead to cell death. But life or death may not be the whole story when it comes to apoptosis. Given the widely conserved nature of various components of apoptosis, perhaps all the small effects are important because they add up to a dying cell that can be readily eaten and quickly discarded. 
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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