A signal from inside the peroxisome initiates its division by promoting the remodeling of the peroxisomal membrane

We define the dynamics of spatial and temporal reorganization of the team of proteins and lipids serving peroxisome division. The peroxisome becomes competent for division only after it acquires the complete set of matrix proteins involved in lipid metabolism. Overloading the peroxisome with matrix proteins promotes the relocation of acyl-CoA oxidase (Aox), an enzyme of fatty acid β-oxidation, from the matrix to the membrane. The binding of Aox to Pex16p, a membrane-associated peroxin required for peroxisome biogenesis, initiates the biosynthesis of phosphatidic acid and diacylglycerol (DAG) in the membrane. The formation of these two lipids and the subsequent transbilayer movement of DAG initiate the assembly of a complex between the peroxins Pex10p and Pex19p, the dynamin-like GTPase Vps1p, and several actin cytoskeletal proteins on the peroxisomal surface. This protein team promotes membrane fission, thereby executing the terminal step of peroxisome division.

[1]  G. Carman,et al.  Roles of phosphatidate phosphatase enzymes in lipid metabolism. , 2006, Trends in biochemical sciences.

[2]  Robert T. Mullen,et al.  Peroxisome biogenesis: the peroxisomal endomembrane system and the role of the ER , 2006, The Journal of cell biology.

[3]  M. Schrader Shared components of mitochondrial and peroxisomal division. , 2006, Biochimica et biophysica acta.

[4]  A. Luini,et al.  The multiple activities of CtBP/BARS proteins: the Golgi view. , 2006, Trends in cell biology.

[5]  Harvey T. McMahon,et al.  Membrane curvature and mechanisms of dynamic cell membrane remodelling , 2005, Nature.

[6]  S. Munro,et al.  Organelle identity and the signposts for membrane traffic , 2005, Nature.

[7]  S. Thoms,et al.  Dynamin‐related proteins and Pex11 proteins in peroxisome division and proliferation , 2005, The FEBS journal.

[8]  S. Subramani,et al.  The control of peroxisome number and size during division and proliferation. , 2005, Current opinion in cell biology.

[9]  R. Youle,et al.  Mitochondrial fission in apoptosis , 2005, Nature Reviews Molecular Cell Biology.

[10]  D. Voelker Bridging gaps in phospholipid transport. , 2005, Trends in biochemical sciences.

[11]  V. Malhotra,et al.  PKCη is required for β1γ2/β3γ2- and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus , 2005, The Journal of cell biology.

[12]  J. Holthuis,et al.  Lipid traffic: floppy drives and a superhighway , 2005, Nature Reviews Molecular Cell Biology.

[13]  C. Gregg,et al.  Dynamic ergosterol- and ceramide-rich domains in the peroxisomal membrane serve as an organizing platform for peroxisome fusion , 2005, The Journal of cell biology.

[14]  W. Wickner,et al.  Interdependent assembly of specific regulatory lipids and membrane fusion proteins into the vertex ring domain of docked vacuoles , 2004, The Journal of cell biology.

[15]  A. Mayer,et al.  Mutual Control of Membrane Fission and Fusion Proteins , 2004, Cell.

[16]  F. Platt,et al.  Glycosphingolipids in endocytic membrane transport. , 2004, Seminars in cell & developmental biology.

[17]  G. van Meer,et al.  Membrane lipids and vesicular traffic. , 2004, Current opinion in cell biology.

[18]  Harvey T. McMahon,et al.  The dynamin superfamily: universal membrane tubulation and fission molecules? , 2004, Nature Reviews Molecular Cell Biology.

[19]  S. Munro Cell biology: Earthworms and lipid couriers , 2003, Nature.

[20]  J. Nunnari,et al.  The Division of Endosymbiotic Organelles , 2003, Science.

[21]  Alberto Luini,et al.  Prefission constriction of Golgi tubular carriers driven by local lipid metabolism: a theoretical model. , 2003, Biophysical journal.

[22]  M. Kozlov,et al.  Protein-lipid interplay in fusion and fission of biological membranes. , 2003, Annual review of biochemistry.

[23]  Honey Chan,et al.  Peroxisome division in the yeast Yarrowia lipolytica is regulated by a signal from inside the peroxisome , 2003, The Journal of cell biology.

[24]  Khashayar Farsad,et al.  Mechanisms of membrane deformation. , 2003, Current opinion in cell biology.

[25]  V. Malhotra,et al.  Cell-cycle-specific Golgi fragmentation: how and why? , 2003, Current opinion in cell biology.

[26]  S. Newmyer,et al.  Auxilin-dynamin interactions link the uncoating ATPase chaperone machinery with vesicle formation. , 2003, Developmental cell.

[27]  E. Kooijman,et al.  Modulation of Membrane Curvature by Phosphatidic Acid and Lysophosphatidic Acid , 2003, Traffic.

[28]  D. Corda,et al.  Phosphoinositides and the golgi complex. , 2002, Current opinion in cell biology.

[29]  P. D. Andrews,et al.  Sla1p couples the yeast endocytic machinery to proteins regulating actin dynamics. , 2002, Journal of cell science.

[30]  V. Bankaitis Slick Recruitment to the Golgi , 2002, Science.

[31]  P. Philippsen,et al.  A role for Vps1p, actin, and the Myo2p motor in peroxisome abundance and inheritance in Saccharomyces cerevisiae , 2001, The Journal of cell biology.

[32]  R. Rachubinski,et al.  Yarrowia lipolytica cells mutant for the peroxisomal peroxin Pex19p contain structures resembling wild-type peroxisomes. , 2001, Molecular biology of the cell.

[33]  L. Machesky,et al.  Abp1p and cortactin, new “hand-holds” for actin , 2001, The Journal of cell biology.

[34]  P. Sluijs,et al.  How proteins move lipids and lipids move proteins , 2001, Nature Reviews Molecular Cell Biology.

[35]  Y. Hannun,et al.  Enzymes of sphingolipid metabolism: from modular to integrative signaling. , 2001, Biochemistry.

[36]  S. Emr,et al.  Isolation of Subcellular Fractions from the Yeast Saccharomyces cerevisiae , 2000, Current protocols in cell biology.

[37]  A. Newton,et al.  The C1 and C2 domains of protein kinase C are independent membrane targeting modules, with specificity for phosphatidylserine conferred by the C1 domain. , 2000, Biochemistry.

[38]  A. Bretscher,et al.  Polarization of cell growth in yeast. , 2000, Journal of cell science.

[39]  A. Bretscher,et al.  Polarization of cell growth in yeast. I. Establishment and maintenance of polarity states. , 2000, Journal of cell science.

[40]  Honey Chan,et al.  Fusion of Small Peroxisomal Vesicles in Vitro Reconstructs an Early Step in the in Vivo Multistep Peroxisome Assembly Pathway of Yarrowia lipolytica , 2000, The Journal of cell biology.

[41]  K. Athenstaedt,et al.  Phosphatidic acid, a key intermediate in lipid metabolism. , 1999, European journal of biochemistry.

[42]  Jean-Marc Nicaud,et al.  Evaluation of Acyl Coenzyme A Oxidase (Aox) Isozyme Function in the n-Alkane-Assimilating YeastYarrowia lipolytica , 1999, Journal of bacteriology.

[43]  R. Schneiter,et al.  Electrospray Ionization Tandem Mass Spectrometry (Esi-Ms/Ms) Analysis of the Lipid Molecular Species Composition of Yeast Subcellular Membranes Reveals Acyl Chain-Based Sorting/Remodeling of Distinct Molecular Species En Route to the Plasma Membrane , 1999, The Journal of cell biology.

[44]  A L Burlingame,et al.  Searching Sequence Databases Over the Internet: Protein Identification Using MS‐Fit , 1998, Current protocols in protein science.

[45]  C.R. Jiménez,et al.  Searching Sequence Databases Over the Internet: Protein Identification Using MS‐Tag , 1998, Current protocols in protein science.

[46]  Jennifer J. Smith,et al.  Pex20p of the Yeast Yarrowia lipolytica Is Required for the Oligomerization of Thiolase in the Cytosol and for Its Targeting to the Peroxisome , 1998, The Journal of cell biology.

[47]  W. Wickner,et al.  LMA1 Binds to Vacuoles at Sec18p (NSF), Transfers upon ATP Hydrolysis to a t-SNARE (Vam3p) Complex, and Is Released during Fusion , 1998, Cell.

[48]  R. Rachubinski,et al.  Enlarged Peroxisomes Are Present in Oleic Acid–grown Yarrowia lipolytica Overexpressing the PEX16 Gene Encoding an Intraperoxisomal Peripheral Membrane Peroxin , 1997, The Journal of cell biology.

[49]  A. Podtelejnikov,et al.  Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[50]  John E. Coligan,et al.  Current Protocols in Protein Science , 1996 .

[51]  V. Titorenko,et al.  Mutations in the PAY5 Gene of the Yeast Yarrowia lipolytica Cause the Accumulation of Multiple Subpopulations of Peroxisomes* , 1996, The Journal of Biological Chemistry.

[52]  V. Titorenko,et al.  Pay32p of the yeast Yarrowia lipolytica is an intraperoxisomal component of the matrix protein translocation machinery , 1995, The Journal of cell biology.

[53]  Michael M. Kozlov,et al.  How proteins produce cellular membrane curvature , 2006, Nature Reviews Molecular Cell Biology.

[54]  G. Marcus,et al.  The eloquent ape: genes, brains and the evolution of language , 2006, Nature Reviews Genetics.

[55]  G. Warren,et al.  Golgi architecture and inheritance. , 2002, Annual review of cell and developmental biology.

[56]  S Subramani,et al.  Import of peroxisomal matrix and membrane proteins. , 2000, Annual review of biochemistry.

[57]  C. A. Teijgeler [Thin-layer chromatography]. , 1962, Pharmaceutisch weekblad.