Pexophagy: The Selective Degradation of Peroxisomes

Peroxisomes are single-membrane-bounded organelles present in the majority of eukaryotic cells. Despite the existence of great diversity among different species, cell types, and under different environmental conditions, peroxisomes contain enzymes involved in β-oxidation of fatty acids and the generation, as well as detoxification, of hydrogen peroxide. The exigency of all eukaryotic cells to quickly adapt to different environmental factors requires the ability to precisely and efficiently control peroxisome number and functionality. Peroxisome homeostasis is achieved by the counterbalance between organelle biogenesis and degradation. The selective degradation of superfluous or damaged peroxisomes is facilitated by several tightly regulated pathways. The most prominent peroxisome degradation system uses components of the general autophagy core machinery and is therefore referred to as “pexophagy.” In this paper we focus on recent developments in pexophagy and provide an overview of current knowledge and future challenges in the field. We compare different modes of pexophagy and mention shared and distinct features of pexophagy in yeast model systems, mammalian cells, and other organisms.

[1]  Y. Sakai,et al.  Yeast Methylotrophy and Autophagy in a Methanol-Oscillating Environment on Growing Arabidopsis thaliana Leaves , 2011, PloS one.

[2]  T. Saigusa,et al.  Phosphorylation of Serine 114 on Atg32 mediates mitophagy , 2011, Molecular biology of the cell.

[3]  M. Morris,et al.  Glycerol 3-Phosphate Alters Trypanosoma brucei Hexokinase Activity in Response to Environmental Change* , 2011, The Journal of Biological Chemistry.

[4]  I. J. van der Klei,et al.  Damaged peroxisomes are subject to rapid autophagic degradation in the yeast Hansenula polymorpha , 2011, Autophagy.

[5]  P. Lazarow Viruses exploiting peroxisomes. , 2011, Current opinion in microbiology.

[6]  Xuejun Jiang,et al.  SNARE Proteins Are Required for Macroautophagy , 2011, Cell.

[7]  J. Rietdorf,et al.  A role for myelin‐associated peroxisomes in maintaining paranodal loops and axonal integrity , 2011, FEBS letters.

[8]  Sebastian A. Wagner,et al.  Phosphorylation of the Autophagy Receptor Optineurin Restricts Salmonella Growth , 2011, Science.

[9]  P. Cossart,et al.  p62 and NDP52 Proteins Target Intracytosolic Shigella and Listeria to Different Autophagy Pathways , 2011, The Journal of Biological Chemistry.

[10]  L. Santambrogio,et al.  Chasing the elusive mammalian microautophagy , 2011, Autophagy.

[11]  D. Klionsky,et al.  Two MAPK-signaling pathways are required for mitophagy in Saccharomyces cerevisiae , 2011, The Journal of cell biology.

[12]  S. Subramani,et al.  Cell-free sorting of peroxisomal membrane proteins from the endoplasmic reticulum , 2011, Proceedings of the National Academy of Sciences.

[13]  Y. Ho,et al.  Intraperoxisomal redox balance in mammalian cells: oxidative stress and interorganellar cross-talk , 2011, Molecular biology of the cell.

[14]  S. Subramani,et al.  Peroxisome assembly: matrix and membrane protein biogenesis , 2011, The Journal of cell biology.

[15]  J. Cregg,et al.  Atg35, a micropexophagy-specific protein that regulates micropexophagic apparatus formation in Pichia pastoris , 2011, Autophagy.

[16]  A. Sibirny,et al.  CCZ1, MON1 and YPT7 genes are involved in pexophagy, the Cvt pathway and non‐specific macroautophagy in the methylotrophic yeast Pichia pastoris , 2011, Cell biology international.

[17]  C. Sasakawa,et al.  Autophagy targeting of Listeria monocytogenes and the bacterial countermeasure , 2011, Autophagy.

[18]  V. Titorenko,et al.  Peroxisome Metabolism and Cellular Aging , 2011, Traffic.

[19]  P. Kim,et al.  The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited independently to bacteria-associated microdomains to target Salmonella to the autophagy pathway , 2011, Autophagy.

[20]  Harald W. Platta,et al.  The phosphoinositide 3-kinase Vps34p is required for pexophagy in Saccharomyces cerevisiae. , 2011, The Biochemical journal.

[21]  Y. Ohsumi,et al.  PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast , 2011, Journal of lipids.

[22]  L. Santambrogio,et al.  Microautophagy of cytosolic proteins by late endosomes. , 2011, Developmental cell.

[23]  Naoki Tamura,et al.  Atg8 regulates vacuolar membrane dynamics in a lipidation-independent manner in Pichia pastoris , 2010, Journal of Cell Science.

[24]  R. Schekman,et al.  A vesicle carrier that mediates peroxisome protein traffic from the endoplasmic reticulum , 2010, Proceedings of the National Academy of Sciences.

[25]  Daniel J. Klionsky,et al.  An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis , 2010, The Journal of cell biology.

[26]  Y. Sakai,et al.  Peroxisomes as dynamic organelles: autophagic degradation , 2010, The FEBS journal.

[27]  S. Jonjić,et al.  Modulation of natural killer cell activity by viruses. , 2010, Current opinion in microbiology.

[28]  F. Inagaki,et al.  Selective Transport of α-Mannosidase by Autophagic Pathways , 2010, The Journal of Biological Chemistry.

[29]  J. Brenman,et al.  High content screening for non-classical peroxisome proliferators. , 2010, International journal of high throughput screening.

[30]  T. Johansen,et al.  FYCO1: Linking autophagosomes to microtubule plus end-directing molecular motors , 2010, Autophagy.

[31]  N. Hacohen,et al.  Peroxisomes Are Signaling Platforms for Antiviral Innate Immunity , 2010, Cell.

[32]  S. Subramani,et al.  A yeast MAPK cascade regulates pexophagy but not other autophagy pathways , 2010, The Journal of cell biology.

[33]  S. Subramani,et al.  Molecular mechanism and physiological role of pexophagy , 2010, FEBS letters.

[34]  T. Gabaldón Peroxisome diversity and evolution , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[35]  G. Bjørkøy,et al.  FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end–directed vesicle transport , 2010, The Journal of cell biology.

[36]  Narendra Duhita,et al.  The origin of peroxisomes: The possibility of an actinobacterial symbiosis. , 2010, Gene.

[37]  S. Subramani,et al.  Roles of Pichia pastoris Uvrag in vacuolar protein sorting and the phosphatidylinositol 3-kinase complex in phagophore elongation in autophagy pathways , 2010, Autophagy.

[38]  G. Los,et al.  Peroxisome Dynamics in Cultured Mammalian Cells , 2009, Traffic.

[39]  A. Roetzer,et al.  Autophagy supports Candida glabrata survival during phagocytosis , 2009, Cellular microbiology.

[40]  Y. Takano,et al.  Atg26-mediated pexophagy and fungal phytopathogenicity , 2009, Autophagy.

[41]  S. Subramani,et al.  Peroxisome size provides insights into the function of autophagy-related proteins. , 2009, Molecular biology of the cell.

[42]  M. Baes,et al.  Peroxisomes, Myelination, and Axonal Integrity in the CNS , 2009, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[43]  Y. Ohsumi,et al.  Mitochondria-anchored receptor Atg32 mediates degradation of mitochondria via selective autophagy. , 2009, Developmental cell.

[44]  D. Klionsky,et al.  Atg32 is a mitochondrial protein that confers selectivity during mitophagy. , 2009, Developmental cell.

[45]  Y. Ohsumi,et al.  Atg17 recruits Atg9 to organize the pre‐autophagosomal structure , 2009, Genes to Cells.

[46]  T. Okuno,et al.  Atg26-Mediated Pexophagy Is Required for Host Invasion by the Plant Pathogenic Fungus Colletotrichum orbiculare[C][W] , 2009, The Plant Cell Online.

[47]  S. Yokota,et al.  Degradation of excess peroxisomes in mammalian liver cells by autophagy and other mechanisms , 2009, Histochemistry and Cell Biology.

[48]  F. Inagaki,et al.  Structural basis of target recognition by Atg8/LC3 during selective autophagy , 2008, Genes to cells : devoted to molecular & cellular mechanisms.

[49]  J. Lippincott-Schwartz,et al.  Inaugural Article: Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes , 2008 .

[50]  Y. Fujiki,et al.  The peroxin Pex14p is involved in LC3-dependent degradation of mammalian peroxisomes. , 2008, Experimental cell research.

[51]  W. Dunn,et al.  The membrane dynamics of pexophagy are influenced by Sar1p in Pichia pastoris. , 2008, Molecular biology of the cell.

[52]  C. Chu,et al.  Mitochondrially localized ERK2 regulates mitophagy and autophagic cell stress , 2008, Autophagy.

[53]  Zhijian Li,et al.  Arp2 links autophagic machinery with the actin cytoskeleton. , 2008, Molecular biology of the cell.

[54]  J. Thevelein,et al.  G‐protein‐coupled receptor Gpr1 and G‐protein Gpa2 of cAMP‐dependent signaling pathway are involved in glucose‐induced pexophagy in the yeast Saccharomyces cerevisiae , 2008, Cell biology international.

[55]  Y. Ohsumi,et al.  Organization of the pre-autophagosomal structure responsible for autophagosome formation. , 2008, Molecular biology of the cell.

[56]  P. Michels,et al.  Turnover of glycosomes during life-cycle differentiation of Trypanosoma brucei , 2008, Autophagy.

[57]  S. Subramani,et al.  PpAtg30 tags peroxisomes for turnover by selective autophagy. , 2008, Developmental cell.

[58]  I. J. van der Klei,et al.  Pex14 is the sole component of the peroxisomal translocon that is required for pexophagy , 2008, Autophagy.

[59]  Y. Ohsumi,et al.  Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae , 2007, FEBS letters.

[60]  C. Duve The origin of eukaryotes: a reappraisal , 2007, Nature Reviews Genetics.

[61]  Chiung-Ying Chang,et al.  Atg19 mediates a dual interaction cargo sorting mechanism in selective autophagy. , 2007, Molecular biology of the cell.

[62]  I. J. van der Klei,et al.  A Peroxisomal Lon Protease and Peroxisome Degradation by Autophagy Play Key Roles in Vitality of Hansenula polymorpha Cells , 2007, Autophagy.

[63]  Y. Ohsumi,et al.  Hierarchy of Atg proteins in pre‐autophagosomal structure organization , 2007, Genes to cells : devoted to molecular & cellular mechanisms.

[64]  D. Klionsky,et al.  Recruitment of Atg9 to the preautophagosomal structure by Atg11 is essential for selective autophagy in budding yeast , 2006, The Journal of cell biology.

[65]  I. J. van der Klei,et al.  Yeast and filamentous fungi as model organisms in microbody research. , 2006, Biochimica et biophysica acta.

[66]  D. Klionsky,et al.  Atg27 is required for autophagy-dependent cycling of Atg9. , 2006, Molecular biology of the cell.

[67]  S. Subramani,et al.  The requirement of sterol glucoside for pexophagy in yeast is dependent on the species and nature of peroxisome inducers. , 2006, Molecular Biology of the Cell.

[68]  Daniel J Klionsky,et al.  Autophagy in organelle homeostasis: peroxisome turnover. , 2006, Molecular aspects of medicine.

[69]  J. M. Thomson,et al.  Role of Vac8 in Cellular Degradation Pathways in Pichia pastoris , 2006 .

[70]  Taku Nishimura,et al.  Role of Vac8 in Formation of the Vacuolar Sequestering Membrane during Micropexophagy , 2006, Autophagy.

[71]  Ronald J A Wanders,et al.  Biochemistry of mammalian peroxisomes revisited. , 2006, Annual review of biochemistry.

[72]  Yasuyoshi Sakai,et al.  PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy , 2006, The Journal of cell biology.

[73]  Olivier Poch,et al.  The evolutionary origin of peroxisomes: an ER-peroxisome connection. , 2006, Molecular biology and evolution.

[74]  Berend Snel,et al.  Origin and evolution of the peroxisomal proteome , 2006, Biology Direct.

[75]  Keiji Tanaka,et al.  Excess Peroxisomes Are Degraded by Autophagic Machinery in Mammals* , 2006, Journal of Biological Chemistry.

[76]  William A. Dunn, Jr.,et al.  PpAtg9 Trafficking During Micropexophagy in Pichia pastoris , 2006, Autophagy.

[77]  J. Cregg,et al.  Atg28, a Novel Coiled-Coil Protein Involved in Autophagic Degradation of Peroxisomes in the Methylotrophic Yeast Pichia pastoris , 2006, Autophagy.

[78]  D. Klionsky,et al.  The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae. , 2005, Molecular biology of the cell.

[79]  A. Burlingame,et al.  Atg19p Ubiquitination and the Cytoplasm to Vacuole Trafficking Pathway in Yeast* , 2005, Journal of Biological Chemistry.

[80]  I. J. van der Klei,et al.  Hansenula polymorpha Vam7p is required for macropexophagy. , 2005, FEMS yeast research.

[81]  Tina Chang,et al.  PpATG9 encodes a novel membrane protein that traffics to vacuolar membranes, which sequester peroxisomes during pexophagy in Pichia pastoris. , 2005, Molecular biology of the cell.

[82]  Arjen M. Krikken,et al.  The Hansenula polymorpha ATG25 Gene Encodes a Novel Coiled-Coil Protein that is Required for Macropexophagy , 2005, Autophagy.

[83]  J. Cregg,et al.  Pexophagy: The Selective Autophagy of Peroxisomes , 2005, Autophagy.

[84]  Y. Sakai,et al.  Intracellular ATP Correlates with Mode of Pexophagy in Pichia pastoris , 2005, Bioscience, biotechnology, and biochemistry.

[85]  Arjen M. Krikken,et al.  Atg8 is Essential for Macropexophagy in Hansenula polymorpha , 2005, Traffic.

[86]  P. Michels,et al.  Peroxisomes, glyoxysomes and glycosomes (Review) , 2005, Molecular membrane biology.

[87]  Y. Ohsumi,et al.  A sorting nexin PpAtg24 regulates vacuolar membrane dynamics during pexophagy via binding to phosphatidylinositol-3-phosphate. , 2004, Molecular biology of the cell.

[88]  Arjen M. Krikken,et al.  Atg21p is essential for macropexophagy and microautophagy in the yeast Hansenula polymorpha , 2004, FEBS letters.

[89]  W. Hol,et al.  Biogenesis of peroxisomes and glycosomes: trypanosomatid glycosome assembly is a promising new drug target. , 2004, FEMS microbiology reviews.

[90]  Arjen M. Krikken,et al.  Hansenula polymorpha Tup1p is important for peroxisome degradation. , 2004, FEMS yeast research.

[91]  I. J. van der Klei,et al.  Microautophagy and macropexophagy may occur simultaneously in Hansenula polymorpha , 2004, FEBS letters.

[92]  J. Cregg,et al.  Sterol glucosyltransferases have different functional roles inPichia pastoris and Yarrowia lipolytica , 2003, Cell biology international.

[93]  M. Osumi,et al.  Modification of a ubiquitin-like protein Paz2 conducted micropexophagy through formation of a novel membrane structure. , 2003, Molecular biology of the cell.

[94]  H. Tabak,et al.  Peroxisomes Start Their Life in the Endoplasmic Reticulum , 2003, Traffic.

[95]  H. Tabak,et al.  Involvement of the endoplasmic reticulum in peroxisome formation. , 2003, Molecular biology of the cell.

[96]  Takeshi Noda,et al.  Peroxisome degradation requires catalytically active sterol glucosyltransferase with a GRAM domain , 2003, The EMBO journal.

[97]  S. Yokota Degradation of normal and proliferated peroxisomes in rat hepatocytes: Regulation of peroxisomes quantity in cells , 2003, Microscopy research and technique.

[98]  J. Kiel,et al.  Selective degradation of peroxisomes in yeasts , 2003, Microscopy research and technique.

[99]  M. Veenhuis,et al.  The Hansenula polymorpha PDD7 gene is essential for macropexophagy and microautophagy. , 2003, FEMS yeast research.

[100]  M. Veenhuis,et al.  The gene is essential for macropexophagy and microautophagy , 2003 .

[101]  D. Valle,et al.  PEX11α Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation , 2002, Molecular and Cellular Biology.

[102]  Arnold H. Buss Pathways , 2002, Journal of personality assessment.

[103]  Jay I. Koepke,et al.  Peroxisome senescence in human fibroblasts. , 2002, Molecular biology of the cell.

[104]  I. J. van der Klei,et al.  Removal of Pex3p Is an Important Initial Stage in Selective Peroxisome Degradation in Hansenula polymorpha * , 2002, The Journal of Biological Chemistry.

[105]  James E. Klaunig,et al.  COMPARATIVE EFFECTS OF PHTHALATE MONOESTERS ON GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND PEROXISOME PROLIFERATION IN RODENT AND PRIMATE HEPATOCYTES , 2002, Journal of toxicology and environmental health. Part A.

[106]  M. Baba,et al.  Paz2 and 13 other PAZ gene products regulate vacuolar engulfment of peroxisomes during micropexophagy , 2002, Genes to cells : devoted to molecular & cellular mechanisms.

[107]  D. Klionsky,et al.  Cvt18/Gsa12 is required for cytoplasm-to-vacuole transport, pexophagy, and autophagy in Saccharomyces cerevisiae and Pichia pastoris. , 2001, Molecular biology of the cell.

[108]  A. Bevan,et al.  GSA11 Encodes a Unique 208-kDa Protein Required for Pexophagy and Autophagy in Pichia pastoris * , 2001, The Journal of Biological Chemistry.

[109]  D. Klionsky,et al.  Cvt9/Gsa9 Functions in Sequestering Selective Cytosolic Cargo Destined for the Vacuole , 2001, The Journal of cell biology.

[110]  Takeshi Noda,et al.  A ubiquitin-like system mediates protein lipidation , 2000, Nature.

[111]  N. Latruffe,et al.  Regulation of the peroxisomal β-oxidation-dependent pathway by peroxisome proliferator-activated receptor α and kinases , 2000 .

[112]  M. Veenhuis,et al.  Isolation of Penicillium chrysogenum PEX1 and PEX6 encoding AAA proteins involved in peroxisome biogenesis , 2000, Applied Microbiology and Biotechnology.

[113]  Y. Fujiki,et al.  Peroxisome biogenesis and peroxisome biogenesis disorders , 2000, FEBS letters.

[114]  N. Macdonald,et al.  Species differences in response to diethylhexylphthalate: suppression of apoptosis, induction of DNA synthesis and peroxisome proliferator activated receptor alpha-mediated gene expression , 2000, Archives of Toxicology.

[115]  D. Klionsky,et al.  Apg9p/Cvt7p Is an Integral Membrane Protein Required for Transport Vesicle Formation in the Cvt and Autophagy Pathways , 2000, The Journal of cell biology.

[116]  D. Klionsky,et al.  Peroxisome degradation in Saccharomyces cerevisiae is dependent on machinery of macroautophagy and the Cvt pathway. , 1999, Journal of cell science.

[117]  J. Cregg,et al.  A Pichia pastoris VPS15 homologue is required in selective peroxisome autophagy , 1999, Current Genetics.

[118]  I. J. van der Klei,et al.  The Hansenula polymorpha PDD1 gene product, essential for the selective degradation of peroxisomes, is a homologue of Saccharomyces cerevisiae Vps34p , 1999, Yeast.

[119]  Daniel E. Warren,et al.  Metabolic control of peroxisome abundance. , 1999, Journal of cell science.

[120]  P. Carmeliet,et al.  A mouse model for Zellweger syndrome , 1997, Nature Genetics.

[121]  D. L. Tuttle,et al.  Glucose-induced microautophagy in Pichia pastoris requires the alpha-subunit of phosphofructokinase. , 1997, Journal of cell science.

[122]  J. Vamecq,et al.  Peroxisome proliferators and peroxisome proliferator activated receptors (PPARs) as regulators of lipid metabolism. , 1997, Biochimie.

[123]  T. Tsukamoto,et al.  A human gene responsible for Zellweger syndrome that affects peroxisome assembly. , 1992, Science.

[124]  S. Gould,et al.  Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase , 1987, The Journal of cell biology.

[125]  S. Gould,et al.  Firefly luciferase is targeted to peroxisomes in mammalian cells. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[126]  S. Yokota Quantitative immunocytochemical studies on differential induction of serine , 1986, Histochemistry.

[127]  P. Baudhuin,et al.  Peroxisomes (microbodies and related particles). , 1966, Physiological reviews.

[128]  Yasunori Watanabea,et al.  SELECTIVE TRANSPORT OF ALPHA-MANNOSIDASE BY AUTOPHAGIC PATHWAYS: STRUCTURAL BASIS FOR CARGO RECOGNITION BY ATG19 AND ATG34 , 2010 .

[129]  S. Yokota,et al.  Induction of peroxisomal Lon protease in rat liver after di-(2-ethylhexyl)phthalate treatment , 2007, Histochemistry and Cell Biology.

[130]  M. Hayashi,et al.  Functional transformation of plant peroxisomes , 2007, Cell Biochemistry and Biophysics.

[131]  J. M. Thomson,et al.  Early and late molecular events of glucose-induced pexophagy in Pichia pastoris require Vac8. , 2006, Autophagy.

[132]  D. Klionsky,et al.  The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. , 2004, Developmental cell.

[133]  N. Latruffe,et al.  Regulation of the peroxisomal beta-oxidation-dependent pathway by peroxisome proliferator-activated receptor alpha and kinases. , 2000, Biochemical pharmacology.

[134]  S. Subramani Components involved in peroxisome import, biogenesis, proliferation, turnover, and movement. , 1998, Physiological reviews.

[135]  D. L. Tuttle,et al.  Glucose-induced microautophagy in Pichia pastoris requires the α-subunit of phosphofructokinase , 1997 .

[136]  C. de Duve The peroxisome in retrospect. , 1996, Annals of the New York Academy of Sciences.

[137]  D. L. Tuttle,et al.  Divergent modes of autophagy in the methylotrophic yeast Pichia pastoris. , 1995, Journal of cell science.

[138]  U. Pfeifer,et al.  [Diurnal rhythm of lysosomal organelle decomposition in liver, kidney and pancreas]. , 1976, Acta histochemica. Supplementband.

[139]  S. Subramani,et al.  Turnover of Organelles by Autophagy in Yeast This Review Comes from a Themed Issue on Membranes and Organelles Edited Atg9 and Its Cycling System the Cvt Pathway Er-phagy , 2022 .

[140]  I. J. van der Klei,et al.  Pexophagy: autophagic degradation of peroxisomes. , 2006, Biochimica et biophysica acta.