Dismantling the autophagic arsenal when it is time to die: concerted AMBRA1 degradation by caspases and calpains

Autophagy
Marco CorazzariMauro Piacentini

Abstract

Under stress conditions cells activate different response pathways which result in cell survival or apoptosis depending on: (1) the nature of the insults, (2) the type, if acute or chronic stress, and (3) how long the stress persists. Generally, autophagy is induced early to sustain cell survival and inhibit cell death. However, adverse conditions are able to overcome autophagy to promote cell death. Increasing evidence suggests that the inhibition of autophagy by the apoptotic machinery has been proposed as one of the crucial events responsible for the irreversible switch from survival to death. The mechanism seems to be related to the selective apoptotic protease-mediated degradation of key autophagic proteins. We recently found that AMBRA1, an important regulator of the autophagic process mediating the initial steps of autophagosome formation, is also irreversibly degraded by the combined activity of caspases and calpains. This phenomenon is not merely a consequence of apoptosis execution but represents a key step required to efficiently promote the autophagic vs apoptosis switch.

Citations

Oct 17, 2012·Oncogene·G M FimiaM Piacentini
Sep 12, 2015·IEEE/ACM Transactions on Computational Biology and Bioinformatics·Tommaso MazzaValerio Pazienza
Nov 24, 2017·Expert Opinion on Therapeutic Targets·Yubin WangMichel Baudry
Jan 15, 2014·Apoptosis : an International Journal on Programmed Cell Death·Subhadip MukhopadhyaySujit Kumar Bhutia
May 12, 2017·Frontiers in Oncology·Marco CorazzariMauro Piacentini

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