Parthanatos

Abstract

Depending upon the particular conditions encountered by a cell, any of a numberof programmed cell death pathways may be triggered. Using strictly morpholog-ical descriptions to segregate one form of programmed cell death from another,Peter Clarke parsed programmed cell death into three principle forms (1): apop-tosis (Type I, see Refs. 2 and 3), autophagic (Type II, see Refs. 4-6), and cyto-plasmic cell death (Type III, with multiple subtypes, see Refs. 2,3,7). With thedefinition of a set of genes in Saccharomyces cerevisiae required for autophagy inthe mid-1990s [genes that were later dubbed Atg genes], a wealth of informationhas been gathered about the role of autophagy in various biological processes inmetazoans by studying the mammalian homologs of yeast Atg genes (5,8,9).Autophagy, a cellular mechanism for bulk delivery of organelles and cytosol to thelysosome for degradation, has been classically studied as a cellular response toamino acid deprivation. More recently, autophagy is being studied in the contextof trophic factor withdrawal, insulin signaling, longevity, innate immunity, neu-rodegeneration, cancer, and programmed cell death (5). Despite the availability ofRNA interference (RNAi) and knockout mice, the debate over whether autophagycan actively participate in the destruction of a mammalian cell has yet to be settled(10). In this review, I summarize the mechanics of autophagy, review importanthistorical (pre-RNAi) literature on autophagic cell death, and highlight some of themost recently published studies that have contributed to our understanding ofautophagic cell death in mammalian cells.