BAXing in the hypersensitive response

Abstract

Most of the cell death pathways that have been characterized in animal systems require caspase activation as a deterministic step. In some cases, this might involve mitochondria participation, whereas others by-pass this organelle and activate caspases using protein–protein interactions. In organisms such as C. elegans, where a simpler set of cell death regulators is known, no evidence for cytochrome c involvement has been found. Thus, this particular mode of cell death activation might be augmented by other types of pathways that bypass mitochondrial involvement in the activation of cell death. The conserved ability of Bax to activate cell death in yeast and plants via its interaction with the mitochondrial membrane is consistent with the view that this organelle can serve as a cell death activator in many eukaryotes. However, the precise details of why Bax localization to these mitochondria leads to cell death remains to be elucidated. A mammalian gene, Bax Inhibitor 1 (BI-1), has been isolated on the basis of its ability to repress Bax-induced yeast cell death15xBax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast. Xu, Q. and Reed, J.C. Mol. Cell. 1998; 1: 337–346Abstract | Full Text | Full Text PDF | PubMedSee all References15. When overexpressed in mammalian cells, cell death induction by several different agents and treatments is suppressed by BI-1, with the exception of Fas-induced cell death, which does not involve mitochondrial participation. Interestingly, possible BI-1 homologs have been found in the Arabidopsis and C. elegans sequence databases, although their homologies to mammalian BI-1 homologs are rather low (29% and 21% identity, respectively). It will be interesting to determine whether mammalian and Arabidopsis BI-1 are able to suppress Bax- induced cell death in plants as well as hypersensitive response cell death. Another key experiment would be to examine whether cytochrome c release into the cytosol is used by plants to activate cell-death-processes, such as the hypersensitive response. This might link the possible participation of plant mitochondria in hypersensitive response cell death10xBax-induced cell death in tobacco is similar to the hypersensitive response. Lacomme, C. and Santa Cruz, S. Proc. Natl. Acad. Sci. U. S. A. 1999; 96: 7956–7961CrossRef | PubMed | Scopus (220)See all References10 to observations that caspase-like protease activity is activated and appears to be necessary for the hypersensitive response13xCaspases and programmed cell death in the hypersensitive response of plants to pathogens. del Pozo, O. and Lam, E. Curr. Biol. 1998; 8: 1129–1132Abstract | Full Text | Full Text PDF | PubMedSee all References13.