Does Autophagy Contribute To Cell Death?

Abstract

Previously published online as an Autophagy E-publication: http://www.landesbioscience.com/journals/autophagy/abstract.php?id=1739 KEY WORDSautophagy, apoptosis, caspase, phagocytosis, type 2 cell death ACKNOWLEDGEMENTSWe apologize in advance to the researchers who were not referenced due to space limitations. J.D. is funded by NIH KO8 CA098419, and is deeply grateful to the mentorship of Dr. Joan Brugge (Harvard Medical School), in whose laboratory he was a postdoctoral fellow. E.B. is supported by NIH grant GM59136. G.K. receives a special grant from the Ligue Nationale contre le Cancer as well as grants from the European Union (Trans-Death). Review Does Autophagy Contribute to Cell Death?ABSTRACT Autophagy (specifically macroautophagy) is an evolutionarily conserved catabolic process where the cytoplasmic contents of a cell are sequestered within double membrane vacuoles, called autophagosomes, and subsequently delivered to the lysosome for degradation. Autophagy can function as a survival mechanism in starving cells. At the same time, extensive autophagy is commonly observed in dying cells, leading to its classification as an alternative form of programmed cell death. The functional contribution of autophagy to cell death has been a subject of great controversy. However, several recent loss-of-function studies of autophagy (atg) genes have begun to address the roles of autophagy in both cell death and survival. Here, we review the emerging evidence in favor of and against autophagic cell death, discuss the possible roles that autophagic degradation might play in dying cells, and identify salient issues for future investigation.

Autophagy and signaling: their role in cell survival and cell death

“…The role of autophagy during cell death has been discussed in recent reviews. 14,15 During apoptosis, the stimulation of autophagy can be either a protective mechanism or a process that contributes to cell death. In the absence of apoptosis, autophagy can trigger a form of cell death known as autophagic cell death or Type II programmed cell death, which is distinct from Type I programmed cell death (apoptosis).…”

Modelling the effect of GRP78 on anti-oestrogen sensitivity and resistance in breast cancer

“…Autophagy is usually considered a pro-survival response, protecting cells against starvation, infectious agents and treatment with anti-cancer drugs. However, under certain circumstances, autophagy can promote death [40,41]. When EnR stress is extensive or sustained, and the UPR fails to restore normal functioning, apoptosis is triggered [19].…”

“…Autophagy is principally an adaptive response to protect cells from stress, but, in certain settings, it can lead to cell death [40,41]. The process is controlled by a set of evolutionarily conserved autophagy-related proteins (ATG proteins).…”

L’entose, mort cellulaire par cannibalisme entre cellules tumorales

“…Cette résistance leur conférerait potentiellement la capacité de survivre au voyage en dehors de la tumeur primaire et de former ainsi des métastases. D'autres processus de mort non-apoptotique, comme la nécrose cellulaire ou l'autophagie par exemple [3], peuvent parfois agir en synergie avec l'apoptose pour occire efficacement une cellule et peuvent aussi compenser une apoptose déficiente [4,5].…”

“…Au cours de l'apoptose, la cellule mourante émet des signaux. En particulier, elle expose sur le feuillet externe de la membrane plasmique des résidus phosphatidylsérine (PS), un phospholipide normalement situé sur son feuillet interne, qui permettront sa reconnaissance, sa phagocytose et son élimina-tion par les macrophages et d'autres [3,4]. Une autre hypothèse, fondée sur l'expression par les cellules d'Ewing de certaines protéines des jonctions serrées (comme ZO-1 ou la claudine) évoque une origine cellulaire épithéliale [5].…”