Nazarko Taras Y, Polupanov Andriy S, Manjithaya Ravi R, Subramani Suresh, Sibirny Andriy A
Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322, USA.
Mol Biol Cell. 2007 Jan;18(1):106-18. doi: 10.1091/mbc.e06-06-0554. Epub 2006 Nov 1.
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 P. 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.
甾醇葡萄糖基转移酶Ugt51/Atg26对于甲醇诱导的毕赤酵母过氧化物酶体的微自噬和巨自噬均至关重要。然而，该蛋白在其他酵母自噬中的作用仍不清楚。我们发现，解脂耶氏酵母中油酸和胺诱导的过氧化物酶体通过不依赖Atg26的巨自噬进行降解。令人惊讶的是，Atg26对于毕赤酵母中油酸和胺诱导的过氧化物酶体的巨自噬也不是必需的，这表明甾醇葡萄糖苷（SG）在自噬中的功能具有物种和过氧化物酶体诱导剂特异性。然而，在缺乏SG的情况下，毕赤酵母中油酸和胺诱导的过氧化物酶体的降解速率降低，这表明毕赤酵母特别利用Atg26进行甾醇转化以增强过氧化物酶体的选择性降解。然而，甲醇诱导的过氧化物酶体显然已经失去了在没有SG的情况下进行降解的冗余能力。我们还表明，毕赤酵母的Vac8犰狳重复蛋白对于甲醇、油酸或胺诱导的过氧化物酶体的巨自噬不是必需的，这使得PpVac8成为第一个已知的微自噬而非巨自噬机制所需的蛋白。Atg26和Vac8在不同自噬条件下功能的独特性表明，不仅自噬诱导剂（如葡萄糖或乙醇），而且过氧化物酶体诱导剂（如甲醇、油酸或伯胺）决定了酵母后续自噬的需求。
