Peroxisome biogenesis disorders: Molecular basis for impaired peroxisomal membrane assembly In metabolic functions and biogenesis of peroxisomes in health and disease

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Review

Fujiki, Yukio^1,2,3  Yagita, Yuichi² 

[1] Kyushu Univ, Fac Sci, Dept Biol, Grad Sch,Higashi Ku, Fukuoka 8128581, Japan

[2] Kyushu Univ, Grad Sch Syst Life Sci, Fukuoka 8128581, Japan

[3] Japan Scoemce amd Technol Agcy, CREST, Tokyo 1020075, Japan

关键词: Peroxisome biogenesis disorder;    Membrane biogenesis;    Peroxin;    CHO cell mutant;    Membrane protein transporter;    Classes I and II import pathway;   

DOI  :  10.1016/j.bbadis.2012.06.004

来源: Elsevier

【 摘 要 】

Peroxisome is a single-membrane organelle in eukaryotes. The functional importance of peroxisomes in humans is highlighted by peroxisome-deficient peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome (ZS). Gene defects of peroxins required for both membrane assembly and matrix protein import are identified: ten mammalian pathogenic peroxins for ten complementation groups of PBDs, are required for matrix protein import; three, Pex3p, Pex16p and Pex19p, are shown to be essential for peroxisome membrane assembly and responsible for the most severe ZS in PBDs of three complementation groups 12, 9, and 14, respectively. Patients with severe ZS with defects of PEX3. PEX16, and PEX19 tend to carry severe mutation such as nonsense mutations, frameshifts and deletions. With respect to the function of these three peroxins in membrane biogenesis, two distinct pathways have been proposed for the import of peroxisomal membrane proteins in mammalian cells: a Pex19p- and Pex3p-dependent class I pathway and a Pex19p- and Pex16p-dependent class II pathway. In class II pathway, Pex19p also forms a soluble complex with newly synthesized Pex3p as the chaperone for Pex3p in the cytosol and directly translocates it to peroxisomes. Pex16p functions as the peroxisomal membrane receptor that is specific to the Pex3p-Pex19p complexes. A model for the import of peroxisomal membrane proteins is suggested, providing new insights into the molecular mechanisms underlying the biogenesis of peroxisomes and its regulation involving Pex3p, Pex19p, and Pex16p. Another model suggests that in Saccharomyces cerevisiae peroxisomes likely emerge from the endoplasmic reticulum. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of peroxisomes in Health and Disease. (C) 2012 Elsevier B.V. All rights reserved.

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