Abstract
Autophagy is a conserved process in which cytoplasmic components are sequestered for degradation in the vacuole/lysosomes in eukaryotic cells. Autophagy is induced under a variety of starvation conditions, such as the depletion of nitrogen, carbon, phosphorus, zinc, and others. However, apart from nitrogen starvation, it remains unclear how these stimuli induce autophagy. In yeast, for example, it remains contentious whether autophagy is induced under carbon starvation conditions, with reports variously suggesting both induction and lack of induction upon depletion of carbon. We therefore undertook an analysis to account for these inconsistencies, concluding that autophagy is induced in response to abrupt carbon starvation when cells are grown with glycerol but not glucose as the carbon source. We found that autophagy under these conditions is mediated by nonselective degradation that is highly dependent on the autophagosome-associated scaffold proteins Atg11 and Atg17. We also found that the extent of carbon starvation-induced autophagy is positively correlated with cells' oxygen consumption rate, drawing a link between autophagy induction and respiratory metabolism. Further biochemical analyses indicated that maintenance of intracellular ATP levels is also required for carbon starvation-induced autophagy and that autophagy plays an important role in cell viability during prolonged carbon starvation. Our findings suggest that carbon starvation-induced autophagy is negatively regulated by carbon catabolite repression.
Highlights
Autophagy is a conserved process in which cytoplasmic components are sequestered for degradation in the vacuole/lysosomes in eukaryotes
Ape1 is transported to the vacuole via autophagy during starvation conditions, where it is converted from the proform to the mature form by vacuolar hydrolases [15]
We investigated how growth conditions affect carbon starvation–induced autophagy in S. cerevisiae
Summary
In this study we employed an assay in which cells were initially grown on synthetic media, comprising a source of carbon, casamino acids, and ammonium sulfate, before being subjected to carbon starvation, whereby cells were transferred to the same medium lacking a source of carbon. We observed that in cells subjected to carbon starvation, the expression of both GFP-Atg (under the control of its endogenous promotor) and Ape did not increase (Fig. 1A, left). Autophagy was induced when cells grown in glycerol medium were subjected to carbon starvation (Fig. 1A, right). Cells grown in glycerol medium showed consistently high expression levels of both GFP-Atg and Ape compared with the expression levels of these proteins in glucose-grown cells (Fig. 1A, right). We observed autophagy induction upon carbon starvation when prototrophic X2180-1 cells were grown in glycerol medium but not glucose medium. These results indicate that carbon starvation–induced autophagy following growth in the presence of glycerol but not glucose is not unique to BY4741 and is unrelated to the auxotrophy of the cells
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