Tam Yuen Yi C, Fagarasanu Andrei, Fagarasanu Monica, Rachubinski Richard A
Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
J Biol Chem. 2005 Oct 14;280(41):34933-9. doi: 10.1074/jbc.M506208200. Epub 2005 Aug 8.
Peroxisomes are dynamic organelles that often proliferate in response to compounds that they metabolize. Peroxisomes can proliferate by two apparent mechanisms, division of preexisting peroxisomes and de novo synthesis of peroxisomes. Evidence for de novo peroxisome synthesis comes from studies of cells lacking the peroxisomal integral membrane peroxin Pex3p. These cells lack peroxisomes, but peroxisomes can assemble upon reintroduction of Pex3p. The source of these peroxisomes has been the subject of debate. Here, we show that the amino-terminal 46 amino acids of Pex3p of Saccharomyces cerevisiae target to a subdomain of the endoplasmic reticulum and initiate the formation of a preperoxisomal compartment for de novo peroxisome synthesis. In vivo video microscopy showed that this preperoxisomal compartment can import both peroxisomal matrix and membrane proteins leading to the formation of bona fide peroxisomes through the continued activity of full-length Pex3p. Peroxisome formation from the preperoxisomal compartment depends on the activity of the genes PEX14 and PEX19, which are required for the targeting of peroxisomal matrix and membrane proteins, respectively. Our findings support a direct role for the endoplasmic reticulum in de novo peroxisome formation.
过氧化物酶体是动态细胞器，常因它们代谢的化合物而增殖。过氧化物酶体可通过两种明显的机制增殖，即现有过氧化物酶体的分裂和过氧化物酶体的从头合成。过氧化物酶体从头合成的证据来自对缺乏过氧化物酶体整合膜过氧化物酶Pex3p的细胞的研究。这些细胞缺乏过氧化物酶体，但在重新引入Pex3p后过氧化物酶体可以组装。这些过氧化物酶体的来源一直是争论的焦点。在这里，我们表明酿酒酵母Pex3p的氨基末端46个氨基酸靶向内质网的一个亚结构域，并启动用于过氧化物酶体从头合成的过氧化物酶体前体区室的形成。体内视频显微镜显示，这个过氧化物酶体前体区室可以导入过氧化物酶体基质和膜蛋白，通过全长Pex3p的持续活性导致真正过氧化物酶体的形成。过氧化物酶体前体区室形成过氧化物酶体取决于PEX14和PEX19基因的活性，这两个基因分别是过氧化物酶体基质和膜蛋白靶向所必需的。我们的发现支持内质网在过氧化物酶体从头形成中起直接作用。
