Similar to multicellular organisms, the yeast Saccharomyces cerevisiae can undergo apoptosis in response to stress. Much of the molecular machinery that executes apoptosis is conserved among yeast and metazoans, but there are some notable differences. For instance, in metazoans the serine protease Omi (also known as HtrA2) is a mitochondrial protein that is released to the cytosol in apoptosis; by contrast, Nma111p (an Htr-like protein that is required for stress-induced apoptosis in S. cerevisiae) localises to the nucleus, suggesting that its role in the apoptotic programme is distinct from that of Omi. On , Birthe Fahrenkrog and colleagues confirm that this is the case. Using heterokaryon assays, they first show that Nma111p does not shuttle between the nucleus and cytoplasm, even under pro-apoptotic conditions. They next identify two clusters of basic residues near the Nma111p N-terminus that form a nuclear localisation sequence (NLS); moreover, mutations in the NLS reduce peroxide-induced apoptosis and lead to enhanced lifespan during chronological ageing. On the basis of these and other data, they conclude that nuclear localisation is a prerequisite for the apoptotic activity of Nma111p. These results underscore the differences between the apoptotic programmes in yeast and metazoans, and emphasise the role of the nucleus in yeast apoptosis.
