ABSTRACT
Depending upon the particular conditions encountered by a cell, any of a number
of 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 the
definition of a set of genes in Saccharomyces cerevisiae required for autophagy in
the mid-1990s [genes that were later dubbed Atg genes], a wealth of information
has been gathered about the role of autophagy in various biological processes in
metazoans by studying the mammalian homologs of yeast Atg genes (5,8,9).
Autophagy, a cellular mechanism for bulk delivery of organelles and cytosol to the
lysosome for degradation, has been classically studied as a cellular response to
amino acid deprivation. More recently, autophagy is being studied in the context
of trophic factor withdrawal, insulin signaling, longevity, innate immunity, neu-
rodegeneration, cancer, and programmed cell death (5). Despite the availability of
RNA interference (RNAi) and knockout mice, the debate over whether autophagy
can 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 important
historical (pre-RNAi) literature on autophagic cell death, and highlight some of the
most recently published studies that have contributed to our understanding of
autophagic cell death in mammalian cells.
