Intracellular ATP correlates with mode of pexophagy in Pichia pastoris

The methylotrophic yeast Pichia pastoris can degrade peroxisomes selectively though two distinct pexophagic pathways, viz., micropexophagy and macropexophagy. These micro- and macropexophagy pathways are induced by adaptation of methanol-grown cells to glucose-containing and ethanol-containing media respectively. However, our understanding of the molecular signal(s) that determine which pathway is activated or repressed in response to environmental changes is limited. In this study, the determinant for these pathways was sought using cells undergoing pexophagy under a variety of conditions. Micropexophagy and macropexophagy were distinguished in living cells by fluorescence microscopy. Our results indicate that glucose and ethanol were not specific inducers of micro- and macropexophagy respectively. Micropexophagy was found to be more sensitive to ATP-depletion than macropexophagy, suggesting that the micropexophagic process requires a higher level of ATP than the macropexophagic process. From these and other results, we postulate that intracellular ATP levels play an important role in determining which pexophagic pathway is activated.