Cell death and the well of the organism.

Abstract

‘‘People always say what we are looking for is ameaning for life…I don’t think that’s what we’relooking for. I think what we’re looking for is theexperience of being alive.’’ Joseph Campbell.In most cultures around the world, the concept of‘‘Death’’ comes along with two other unpleasant words:‘‘Disease’’ and ‘‘Sorrow’’. Developmental biologists seemto view death in their own way: at the microscopic realm ofmulticellular organisms, the death of an individual or evena group of cells can be not only beneficial but oftenrequired for their proper development and then for themaintenance of the homeostasis during young and adultlife. It is estimated that 50–70 billion cells die every day ina healthy adult human being due to constant cellularrenewal that occurs in certain tissues, such as skin, intes-tine, and the hematopoietic system [1]. These numbers areso impressive that they may represent a total body weightof an individual every year, or the accumulation of 2 tonsof bone marrow and lymph nodes and 16 km of intestine inan 80-year-old human being [2].The physiologic form of cell death that we generallyobserved during development was first called ‘‘pro-grammed cell death’’ (PCD) [3] and then ‘‘apoptosis’’ [4].With time, PCD was proven to be controlled by an evo-lutionarily conserved molecular program. The discovery ofthe specific genes involved in the regulation of organdevelopment and programmed cell death in the nematodeC. elegans awarded Sydney Brenner, John E. Sulston, andH. Robert Horvitz the Nobel Prize in Physiology or Med-icine in 2002. Nowadays, we recognize many forms of celldeath and fairly understand the central molecular mecha-nism that regulates them. Importantly, to avoid confusionin the literature, the Nomenclature Committee on CellDeath (NCCD) recently developed a guideline directed toauthors, reviewers, and editors with recommendations forthe use of terms related to the field of cell death [5]. TheNCCD also proposed new criteria for the definition of thetypes of cell death.In this issue of Cellular and Molecular Life Sciences,review articles will cover the classic and unconventionalaspects of molecular pathways that control apoptosis, aswell as other forms of cell death such as necrosis, pyrop-tosis, and death by autophagy. Vandenabeele andcollaborators use the TNFR signaling to reveal themolecular switches involved in the control of survival,apoptosis, or necrosis. They highlight the interplaybetween RIP1, NF-jB, and caspase activation to the out-come of TNFR signaling. Fimia and Piacentini focus theirreview on the molecular control of autophagy and discussthe implication of this process to either the preservation ofcell viability or to the induction of cell death, in particularin the scenario of tumor cells. Ricci and collaboratorsexplored the role of mitochondria in cell death and care-fully review the control of mitochondrial outer membranepermeabilization (MOMP) by Bcl-2 family members. Theyunderscore the importance of mitochondria in inducing(caspase-dependent) apoptosis and point out that mito-chondria also have a role in what they call caspase-independent cell death (CICD). Autret and Martin, on theother hand, draw attention to another aspect of the mito-chondrial physiology—the process of dynamic remodeling