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Vol. 18, Issue 1, 106-118, January 2007

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The Requirement of Sterol Glucoside for Pexophagy in Yeast Is Dependent on the Species and Nature of Peroxisome Inducers

Taras Y. Nazarko^*,, Andriy S. Polupanov, Ravi R. Manjithaya^*, Suresh Subramani^*, and Andriy A. Sibirny^,

*Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322; Department of Molecular Genetics and Biotechnology, Institute of Cell Biology, National Academy of Sciences of Ukraine, 79005 Lviv, Ukraine; and Department of Metabolic Engineering, Rzeszow University, Cwiklinskiej 2, Rzeszow 3-601, Poland

Submitted June 26, 2006; Revised October 13, 2006; Accepted October 19, 2006
Monitoring Editor: Benjamin Glick

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.

This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-06-0554) on November 1, 2006.

Address correspondence to: Suresh Subramani (ssubramani{at}ucsd.edu)

Abbreviations used: AOX, alcohol oxidase; Atg, autophagy-related; Cvt, cytoplasm-to-vacuole targeting; EYFP, enhanced yellow fluorescent protein; MIPA, micropexophagic membrane apparatus; PAS, preautophagosomal structure; PiB, phosphate buffer; SG, sterol glucoside; THI, thiolase; VSM, vacuolar sequestering membrane.