The Great Debate: Regulated Cell Death in Fungi and the Role of Metacaspases

Caspases orchestrate metazoan apoptosis, regulating processes such as embryogenesis, the death of old and infected cells and immune tolerance. Structural orthologs of caspases have been identified in bacteria, plants, protists and fungi and regulated cell death has been demonstrated in these organisms. This led some researchers to conclude that fungal metacaspases might perform a similar function to caspases. This review discusses regulated cell death, beginning with an account of RCD and the central role of caspases in mammalian RCD. It goes on to give examples of RCD in fungi, compares the structure and activity of caspase orthologs and outlines examples of metacaspase-dependent and metacaspase-independent cell death in fungi, focusing on S. cerevisiae. Finally, it addresses the question “are metacaspases caspases?”, identifies alternative cell death proteases and recommends future research objectives.