Peroxisome biogenesis and human peroxisome-deficiency disorders.
Peroxisome biogenesis and human peroxisome-deficiency disorders.
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DOI：
10.2183/pjab.92.463
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Fujiki Y
中科院分区：
文献类型：
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作者：
Fujiki Y
过氧化物酶体是一种单膜结合的普遍存在的细胞器，含有一百种不同的酶，催化各种代谢途径，如极长链脂肪酸的β-氧化和缩醛磷脂的合成。为了研究过氧化物酶体的生物合成以及包括Zellweger综合征在内的人类过氧化物酶体生物合成障碍（PBDs），我们分离了十几种不同互补群的中国仓鼠卵巢（CHO）细胞突变体作为模型实验系统。利用CHO细胞突变体的快速功能互补分析，成功克隆了编码过氧化物酶体组装所需的过氧化物酶的PEX基因，为完成PBD致病基因的克隆做出了重要贡献。过氧化物酶分为三组：1）过氧化物酶，包括Pex 3 p、Pex 16 p和Pex 19 p，通过Pex 19 p和Pex 3 p依赖的I类途径以及Pex 19 p和Pex 16 p依赖的II类途径负责过氧化物酶体膜生物合成; 2）在基质蛋白输入中起作用的过氧化物酶; 3）参与过氧化物酶体分裂的过氧化物酶，如Pex 11 p β，其中DLP 1、Mff和Fis 1协同发挥作用。
Peroxisome is a single-membrane-bounded ubiquitous organelle containing a hundred different enzymes that catalyze various metabolic pathways such as β-oxidation of very long-chain fatty acids and synthesis of plasmalogens. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders (PBDs) including Zellweger syndrome, more than a dozen different complementation groups of Chinese hamster ovary (CHO) cell mutants impaired in peroxisome biogenesis are isolated as a model experimental system. By taking advantage of rapid functional complementation assay of the CHO cell mutants, successful cloning of PEX genes encoding peroxins required for peroxisome assembly invaluably contributed to the accomplishment of cloning of pathogenic genes responsible for PBDs. Peroxins are divided into three groups: 1) peroxins including Pex3p, Pex16p and Pex19p, are responsible for peroxisome membrane biogenesis via Pex19p- and Pex3p-dependent class I and Pex19p- and Pex16p-dependent class II pathways; 2) peroxins that function in matrix protein import; 3) those such as Pex11pβ are involved in peroxisome division where DLP1, Mff, and Fis1 coordinately function.