Dataset Information

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 TRAIL in either Type I or II cells. These data illustrate that differences in autophagy in a cell population determine cell fate in a stimulus- and cell-type-specific manner. This example of selective autophagy of an apoptosis regulator may represent a general mechanism for context-specific regulation of cell fate by autophagy.

SUBMITTER: Gump JM

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

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gump Jacob M JM Staskiewicz Leah L Morgan Michael J MJ Bamberg Alison A Riches David W H DW Thorburn Andrew A

Nature cell biology 20131208 1

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 tha ...[more]

PMID: 24316673

Similar Datasets

Project description:Cytosolic (U-IN-2) or apoplasmic (U-IN-1) targeting of yeast invertase in potato tubers leads to a reduction in sucrose and an increase in glucose content, but specific phenotypical changes are dependent on the subcellular targeting of the enzyme. Cytosolic expression leads to a more severe phenotype with the most striking aspects being reduced starch content and increased respiration. Despite extensive research, the regulatory mechanisms leading to these changes remain obscure. Recent technological advancements regarding potato transcriptional and genomic research presented us with the opportunity to revisit these lines and perform detailed gene expression analysis, in combination with extensive metabolic profiling, to identify regulatory networks underlying the observed changes. Our results indicate that in both genotypes reduced UDP-glucose production is associated with a reduced expression of cell wall biosynthetic genes. In addition, U-IN-1 tubers are characterized by elevated expression of senescence-associated genes, coupled to reduced expression of genes related to photosynthesis and the cytoskeleton. We provide evidence that increased respiration, observed specifically in U-IN-2 tubers, might be due to sugar signaling via released trehalose-6-phosphate inhibition of the SnRK1 complex. In both genotypes, expression of the plastidic glucose-6-phosphate transporter (GPT) is significantly down-regulated. This leads to a shift in the cytosolic to plastidic glucose-6-phosphate ratio and hence might limit starch synthesis but also the oxidative pentose phosphate pathway. This might explain the observed changes in several additional plastid localized pathways, most notably reduced expression of fatty acid biosynthetic genes and an accumulation of shikimate. Interestingly, a strict negative correlation between invertase and GPT expression could be observed in a wide range of potato tubers. This reciprocal regulation may be part of a more general switch controlling energy versus storage metabolism, suggesting that the fate of assimilate utilization is coordinated at the level of sucrose degradation.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets