Recently, we showed that the requirement of sterol glucoside (SG) during pexophagy in yeasts is dependent on the species and the nature of peroxisome inducers. Atg26, the enzyme that converts sterol to SG, is essential for degradation of very large methanol-induced peroxisomes, but only partly required for degradation of smaller-sized oleate- and amine-induced peroxisomes in Pichia pastoris. Moreover, oleate- and amine-induced peroxisomes of another yeast, Yorrowia lipolytica, are degraded by an Atg26-independent mechanism. The same is true for degradation of oleate-induced peroxisomes in Saccharomyces cerevisiae. Here, we review our findings on the specificity of Atg26 function in pexophagy and extend our observations to the role of SG in the cytoplasm to vacuole targeting (Cvt) pathway and bulk autophagy. The results presented here and elsewhere indicate that Atg26 might increase the efficacy of all autophagy related pathways in P pastoris, but not in other yeasts. Recently, it was shown that P pastoris Atg26 (PpAtg26) is required for elongation of the pre-autophagosomal structure (PAS) into the micropexophagic membrane apparatus (MIPA) during micropexophagy. Therefore, we speculate that SG might facilitate elongation of any double membrane from the PAS and this enhancer function of SG becomes essential when extremely large double membranes are formed.

Sterol glucosyltransferase, Ugt51/Atg26, is essential for both micropexophagy and macropexophagy of methanol-induced peroxisomes in Pichia pastoris. However, the role of this protein in pexophagy in other yeast remained unclear. We show that oleate- and amine-induced peroxisomes in Yarrowia lipolytica are degraded by Atg26-independent macropexophagy. Surprisingly, Atg26 was also not essential for macropexophagy of oleate- and amine-induced peroxisomes in A pastoris, suggesting that the function of sterol glucoside (SG) in pexophagy is both species and peroxisome inducer specific. However, the rates of degradation of oleate- and amine-induced peroxisomes in P. pastoris were reduced in the absence of SG, indicating that P. pastoris specifically uses sterol conversion by Atg26 to enhance selective degradation of peroxisomes. However, methanol-induced peroxisomes apparently have lost the redundant ability to be degraded without SG. We also show that the P. pastoris Vac8 armadillo repeat protein is not essential for macropexophagy of methanol-, oleate-, or amine-induced peroxisomes, which makes PpVac8 the first known protein required for the micropexophagy, but not for the macropexophagy, machinery. The uniqueness of Atg26 and Vac8 functions under different pexophagy conditions demonstrates that not only pexophagy inducers, such as glucose or ethanol, but also the inducers of peroxisomes, such as methanol, oleate, or primary amines, determine the requirements for subsequent pexophagy in yeast.