Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels.

ABSTRACT: Macroautophagy is thought to protect against apoptosis; however, underlying mechanisms are poorly understood. We examined how autophagy affects canonical death receptor-induced mitochondrial outer membrane permeabilization (MOMP) and apoptosis. MOMP occurs at variable times in a population of cells, and this is delayed by autophagy. Additionally, autophagy leads to inefficient MOMP, after which some cells die through a slower process than typical apoptosis and, surprisingly, can recover and divide afterward. These effects are associated with p62/SQSTM1-dependent selective autophagy causing PUMA levels to be kept low through an indirect mechanism whereby autophagy affects constitutive levels of PUMA mRNA. PUMA depletion is sufficient to prevent the sensitization to apoptosis that occurs whe

SUBMITTER: Thorburn J 

PROVIDER: S-EPMC3992854 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature