Autophagy variation within a cell population determines cell fate through selective degradation of Fap-1.

ABSTRACT: Autophagy regulates cell death both positively and negatively, but the molecular basis for this paradox remains inadequately characterized. We demonstrate here that transient cell-to-cell variations in autophagy can promote either cell death or survival depending on the stimulus and cell type. By separating cells with high and low basal autophagy using flow cytometry, we demonstrate that autophagy determines which cells live or die in response to death receptor activation. We have determined that selective autophagic degradation of the phosphatase Fap-1 promotes Fas apoptosis in Type I cells, which do not require mitochondrial permeabilization for efficient apoptosis. Conversely, autophagy inhibits apoptosis in Type II cells (which require mitochondrial involvement) or on treatment with TR

SUBMITTER: Gump JM 

PROVIDER: S-EPMC3876036 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature