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

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.

journal_name

Autophagy

journal_title

Autophagy

authors

Corazzari M,Fimia GM,Piacentini M

doi

10.4161/auto.20671

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

1255-7

issue

8

eissn

1554-8627

issn

1554-8635

pii

20671

journal_volume

8

pub_type

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