Pex11pβ-mediated growth and division of mammalian peroxisomes follows a maturation pathway

Pex11pβ-mediated growth and division of mammalian peroxisomes follows a maturation pathway
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DOI:
10.1242/jcs.062109
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发表时间:
2010-08-15
影响因子:
4
通讯作者:
Schrader, Michael
Schrader, Michael
中科院分区:
生物学2区
文献类型:
--
作者:
Delille, Hannah K.;Agricola, Brigitte;Schrader, Michael

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过氧化物酶体是普遍存在的亚细胞器,其通过生长和分裂繁殖,但也可以通过内质网重新形成。过氧化物酶体在哺乳动物细胞中的生长和分裂包括伸长、膜收缩和最终的分裂。动力蛋白样蛋白(DLP 1/Drp 1)及其膜接头Fis 1在过氧化物酶体分裂的后期发挥作用,而膜过氧化物酶Pex 11 p β似乎在该过程的早期起作用。我们已经发现,Pex 11 p β-YFPm融合蛋白可用作进一步剖析过氧化物酶体生长和分裂的特异性工具。Pex 11 p β-YFPm抑制过氧化物酶体的分割和分裂,但导致形成由球状结构域和管状延伸组成的前过氧化物酶体膜结构。过氧化物酶体基质和膜蛋白被靶向到过氧化物酶体结构的不同区域。Pex 11 p β介导的膜形成是在预先存在的过氧化物酶体上启动的,这表明生长和分裂遵循多步成熟途径,哺乳动物过氧化物酶体的形成比预先存在的细胞器的简单分裂更复杂。过氧化物酶体的形成和膜变形的机制,这些研究结果的影响进行了讨论。
Peroxisomes are ubiquitous subcellular organelles, which multiply by growth and division but can also form de novo via the endoplasmic reticulum. Growth and division of peroxisomes in mammalian cells involves elongation, membrane constriction and final fission. Dynamin-like protein (DLP1/Drp1) and its membrane adaptor Fis1 function in the later stages of peroxisome division, whereas the membrane peroxin Pex11p beta appears to act early in the process. We have discovered that a Pex11p beta-YFPm fusion protein can be used as a specific tool to further dissect peroxisomal growth and division. Pex11p beta-YFPm inhibited peroxisomal segmentation and division, but resulted in the formation of pre-peroxisomal membrane structures composed of globular domains and tubular extensions. Peroxisomal matrix and membrane proteins were targeted to distinct regions of the peroxisomal structures. Pex11p beta-mediated membrane formation was initiated at pre-existing peroxisomes, indicating that growth and division follows a multistep maturation pathway and that formation of mammalian peroxisomes is more complex than simple division of a pre-existing organelle. The implications of these findings on the mechanisms of peroxisome formation and membrane deformation are discussed.