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Caspase-independent apoptosis – the eyes have it

Classic programmed cell death (PCD) involves activation of caspases. Increasing evidence, however, suggests that caspase-independent pathways also exist. Nuclear translocation of the mitochondrial flavoprotein apoptosis-inducing factor (AIF) might be key to one such pathway, but its role is controversial. Karl Csaky and co-workers now provide strong evidence for a caspase-independent AIF pathway in retinal pigment epithelial (RPE) cells, which undergo oxidative-stress-induced PCD in several degenerative diseases (see p. 1915). Comparing oxidant-induced PCD of U937 leukaemia cells and ARPE-19 RPE cells, the authors observe that U937 cells exhibit cleavage of caspase-3 and caspase-9 and DNA laddering – characteristics of caspase-dependent PCD. By contrast, they see none of this in ARPE-19 cells, although the cells show other signs of PCD, such as mitochondrial depolarization and membrane blebbing. Csaky and co-workers note that AIF translocates to the nucleus in the ARPE-19 cells and that this can be inhibited by pretreatment with hepatocyte growth factor (HGF/SCF), which protects the cells from PCD. If AIF rather than caspases indeed drives PCD in RPE cells, the therapeuticpotential of caspase inhibitors for retinal degenerative diseases will be limited.

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Related articles in JCS:

Oxidant-induced cell death in retinal pigment epithelium cells mediated through the release of apoptosis-inducing factor

Congxiao Zhang, Judit Baffi, Scott W. Cousins, and Karl G. Csaky
JCS 2003 116: 1915-1923. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?