Macropexophagy

Macropexophagy is a selective autophagic process in which peroxisomes are degraded inside the vacuole or lysosome via the macroautophagy pathway. It is one form of pexophagy, a broader category that controls peroxisome abundance in response to cellular conditions.

In macropexophagy, peroxisomes are recognized on their surface by peroxisome-associated receptors, such as Atg30 in several yeasts (with Atg36 serving as a receptor in some species). Recognition leads to recruitment of the autophagy machinery and the formation of an isolation membrane that engulfs one or more peroxisomes to form autophagosome-like vesicles. These vesicles then fuse with the vacuole, where peroxisomal contents are degraded by vacuolar hydrolases. This mode requires core autophagy-related (ATG) genes and is distinguishable from micropexophagy by its use of autophagosome-like sequestration rather than direct vacuolar engulfment.

Micropexophagy is the related alternative where the vacuole engulfs peroxisomes directly through invagination of the vacuolar membrane, without the formation of a canonical autophagosome. Both macropexophagy and micropexophagy are triggered by nutrient or metabolic shifts that render peroxisomes unnecessary, such as changes in carbon sources that reduce reliance on fatty acid or methanol metabolism.

The process has been studied in yeast species that rely on peroxisomes for metabolism, including Hansenula polymorpha and Pichia pastoris, as well as in Saccharomyces cerevisiae. Understanding macropexophagy contributes to broader insights into organelle turnover and cellular adaptation to environmental changes.