title: The evolution of cell death programs as prerequisites of multicellularity.
abstract: One of the hallmarks of multicellularity is that the individual cellular fate is sacrificed for the benefit of a higher order of life-the organism. The accidental death of cells in a multicellular organism results in swelling and membrane-rupture and inevitably spills cell contents into the surrounding tissue with deleterious effects for the organism. To avoid this form of necrotic death the cells of metazoans have developed complex self-destruction mechanisms, collectively called programmed cell death, which see to an orderly removal of superfluous cells. Since evolution never invents new genes but plays variations on old themes by DNA mutations, it is not surprising, that some of the genes involved in metazoan death pathways apparently have evolved from homologues in unicellular organisms, where they originally had different functions. Interestingly some unicellular protozoans have developed a primitive form of non-necrotic cell death themselves, which could mean that the idea of an altruistic death for the benefit of genetically identical cells predated the invention of multicellularity. The cell death pathways of protozoans, however, show no homology to those in metazoans, where several death pathways seem to have evolved in parallel. Mitochondria stands at the beginning of several death pathways and also determines, whether a cell has sufficient energy to complete a death program. However, the endosymbiotic bacterial ancestors of mitochondria are unlikely to have contributed to the recent mitochondrial death machinery and therefore, these components may derive from mutated eukaryotic precursors and might have invaded the respective mitochondrial compartments. Although there is no direct evidence, it seems that the prokaryotic-eukaryotic symbiosis created the space necessary for sophisticated death mechanisms on command, which in their distinct forms are major factors for the evolution of multicellular organisms.
authors.affiliation: Institute of Clinical Pathology, University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: Simone
authors.initials: S
authors.lastname: Huettenbrenner
authors.forename: Susanne
authors.initials: S
authors.lastname: Maier
authors.forename: Christina
authors.initials: C
authors.lastname: Leisser
authors.forename: Doris
authors.initials: D
authors.lastname: Polgar
authors.forename: Stephan
authors.initials: S
authors.lastname: Strasser
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.forename: Georg
authors.initials: G
authors.lastname: Krupitza
mesh_terms: D000818:Animals; D017209:Apoptosis; D005075:Biological Evolution; D006801:Humans; D008928:Mitochondria / Q000502:physiology; D009336:Necrosis