title: The role of the endoplasmic reticulum in peroxisome biogenesis.
abstract: Peroxisomes are essential cellular organelles involved in lipid metabolism. Patients affected by severe peroxisome biogenesis disorders rarely survive their first year. Genetic screens in several model organisms have identified more than 30 PEX genes that are required for the formation of functional peroxisomes. Despite significant work on the PEX genes, the biogenic origin of peroxisomes remains controversial. For at least two decades, the prevailing model postulated that peroxisomes propagate by growth and fission of preexisting peroxisomes. In this review, we focus on the recent evidence supporting a new, semiautonomous model of peroxisomal biogenesis. According to this model, peroxisomal membrane proteins (PMPs) traffic from the endoplasmic reticulum (ER) to the peroxisome by a vesicular budding, targeting, and fusion process while peroxisomal matrix proteins are imported into the organelle by an autonomous, posttranslational mechanism. We highlight the contradictory conclusions reached to answer the question of how PMPs are inserted into the ER. We then review what we know and what still remains to be elucidated about the mechanism of PMP exit from the ER and the contribution of preperoxisomal vesicles to mature peroxisomes. Finally, we discuss discrepancies in our understanding of de novo peroxisome biogenesis in wild-type cells. We anticipate that resolving these key issues will lead to a more complete picture of peroxisome biogenesis.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
authors: Lazar
authors: L
authors: Dimitrov
authors: Sheung Kwan
authors: SK
authors: Lam
authors: Randy
authors: R
authors: Schekman
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D008565:Membrane Proteins
references: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15785-90
references: 18836080
references: Proc Natl Acad Sci U S A. 1978 Oct;75(10):5066-70
references: 368807
references: J Cell Biol. 2000 Mar 6;148(5):931-44
references: 10704444
references: J Cell Biol. 1991 Sep;114(6):1167-78
references: 1894692
references: J Biol Chem. 1996 Feb 16;271(7):3706-13
references: 8631984
references: Physiol Rev. 1998 Jan;78(1):171-88
references: 9457172
references: Am J Hum Genet. 1998 Dec;63(6):1622-30
references: 9837814
references: Annu Rev Genet. 2000;34:623-652
references: 11092841
references: J Cell Biol. 2000 Jan 10;148(1):29-44
references: 10629216
references: FEBS Lett. 1997 Jul 7;411(1):133-9
references: 9247158
references: J Cell Biol. 2000 Jun 26;149(7):1345-60
references: 10871277
references: J Cell Biol. 2007 Jul 30;178(3):399-410
references: 17646399
references: J Cell Biol. 2004 Jan 5;164(1):57-67
references: 14709540
references: J Cell Biol. 1972 May;53(2):532-60
references: 4112543
references: Nat Rev Mol Cell Biol. 2010 Dec;11(12):885-90
references: 21081964
references: Cell Mol Life Sci. 2002 Jun;59(6):1058-69
references: 12169017
references: J Cell Biol. 2006 May 22;173(4):521-32
references: 16717127
references: Cell. 2008 Aug 22;134(4):634-45
references: 18724936
references: Curr Opin Microbiol. 1998 Apr;1(2):232-7
references: 10066486
references: Biochim Biophys Acta. 2006 Dec;1763(12):1733-48
references: 17055079
references: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12027-31
references: 11593013
references: EMBO J. 1991 Nov;10(11):3255-62
references: 1680677
references: J Cell Biol. 1999 Jan 25;144(2):255-66
references: 9922452
references: Trends Biochem Sci. 1998 Jul;23(7):231-3
references: 9697407
references: Cell. 2012 Apr 13;149(2):397-409
references: 22500805
references: J Cell Biol. 2004 Mar 15;164(6):863-75
references: 15007061
references: Yeast. 1992 Aug;8(8):613-28
references: 1441741
references: Eur J Cell Biol. 2010 Dec;89(12):947-54
references: 20655617
references: J Cell Sci. 2001 Jun;114(Pt 11):2199-204
references: 11493655
references: Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12746-51
references: 21768384
references: J Biol Chem. 2005 Oct 7;280(40):34350-7
references: 16100114
references: Mol Biol Cell. 2010 Jun 15;21(12):2057-65
references: 20427571
references: Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21523-8
references: 21098289
references: Traffic. 2012 Apr;13(4):599-609
references: 22212716
references: J Biol Chem. 2005 Oct 14;280(41):34933-9
references: 16087670
references: J Cell Biol. 1998 Apr 20;141(2):373-83
references: 9548716
references: J Cell Biol. 2008 Dec 29;183(7):1275-86
references: 19114594
references: Annu Rev Cell Dev Biol. 2005;21:529-50
references: 16212506
references: J Cell Biol. 1987 Dec;105(6 Pt 2):2923-31
references: 3480287
references: Mol Cell. 2003 Mar;11(3):635-46
references: 12667447
references: Curr Biol. 2010 Jul 27;20(14):1310-5
references: 20619655
references: Nat Rev Mol Cell Biol. 2010 Sep;11(9):644-54
references: 20717147
references: J Bacteriol. 1992 Aug;174(15):4943-51
references: 1629154
references: Proc Natl Acad Sci U S A. 1989 Jul;86(14):5419-23
references: 2568633
references: Mol Biol Cell. 2007 Mar;18(3):839-49
references: 17192411
references: Nat Cell Biol. 2011 Dec 22;14(1):20-8
references: 22193160
references: Curr Biol. 2008 Jan 22;18(2):102-8
references: 18207745
references: Immunol Rev. 2005 Oct;207:8-18
references: 16181323
references: Curr Opin Cell Biol. 2008 Aug;20(4):393-400
references: 18619829
references: Annu Rev Cell Biol. 1985;1:489-530
references: 3916321
references: Mol Cell Biol. 1998 Jan;18(1):616-28
references: 9418908
references: J Cell Biol. 1993 Dec;123(6 Pt 2):1717-25
references: 8276892
references: J Cell Biol. 2000 Aug 21;150(4):881-6
references: 10953011
references: Curr Genet. 1995 Aug;28(3):248-57
references: 8529271
references: Curr Biol. 1998 Apr 23;8(9):R299-302
references: 9560335
references: Cell. 2005 Jul 15;122(1):85-95
references: 16009135
references: J Cell Biol. 2000 Jun 12;149(6):1171-8
references: 10851015
references: Mol Cell. 2002 Apr;9(4):789-98
references: 11983170
references: Mol Biol Cell. 2004 Jul;15(7):3406-17
references: 15133130
references: Proc Natl Acad Sci U S A. 2011 May 31;108(22):9113-8
references: 21576455
references: EMBO J. 2000 Jan 17;19(2):223-33
references: 10637226