Hutchins M U, Veenhuis M, Klionsky D J
University of California, Davis, Section of Microbiology, Davis, CA 95616, USA.
J Cell Sci. 1999 Nov;112 ( Pt 22):4079-87. doi: 10.1242/jcs.112.22.4079.
Organelle biogenesis and turnover are necessary to maintain biochemical processes that are appropriate to the needs of the eukaryotic cell. Specific degradation of organelles in response to changing environmental cues is one aspect of achieving proper metabolic function. For example, the yeast Saccharomyces cerevisiae adjusts the level of peroxisomes in response to differing nutritional sources. When cells are grown on oleic acid as the sole carbon source, peroxisome biogenesis is induced. Conversely, a subsequent shift to glucose-rich or nitrogen-limiting conditions results in peroxisome degradation. The degradation process, pexophagy, requires the activity of vacuolar hydrolases. In addition, peroxisome degradation is specific. Analyses of cellular marker proteins indicate that peroxisome degradation under these conditions occurs more rapidly and to a greater extent than mitochondrial, Golgi, or cytosolic protein delivery to the vacuole by the non-selective autophagy pathway. To elucidate the molecular mechanism of selective peroxisome degradation, we examined pexophagy in mutants that are defective in autophagy (apg) and the selective targeting of aminopeptidase I to the vacuole by the cytoplasm to vacuole targeting (Cvt) pathway. Inhibition of peroxisome degradation in cvt and apg mutants indicates that these pathways overlap and that peroxisomes are delivered to the vacuole by a mechanism that utilizes protein components of the Cvt/autophagy pathways.
细胞器的生物发生和更新对于维持适合真核细胞需求的生化过程是必要的。响应不断变化的环境线索对细胞器进行特异性降解是实现适当代谢功能的一个方面。例如，酿酒酵母会根据不同的营养来源调整过氧化物酶体的水平。当细胞以油酸作为唯一碳源生长时，过氧化物酶体生物发生被诱导。相反，随后转向富含葡萄糖或氮限制的条件会导致过氧化物酶体降解。这种降解过程，即过氧化物酶体自噬，需要液泡水解酶的活性。此外，过氧化物酶体降解具有特异性。对细胞标记蛋白的分析表明，在这些条件下过氧化物酶体的降解比通过非选择性自噬途径将线粒体、高尔基体或胞质蛋白递送至液泡的速度更快、程度更大。为了阐明选择性过氧化物酶体降解的分子机制，我们在自噬缺陷（apg）突变体以及通过细胞质到液泡靶向（Cvt）途径将氨肽酶I选择性靶向液泡的突变体中研究了过氧化物酶体自噬。在cvt和apg突变体中过氧化物酶体降解的抑制表明这些途径存在重叠，并且过氧化物酶体通过一种利用Cvt/自噬途径蛋白质成分的机制被递送至液泡。
