Abstract
Peroxisomal metabolism and its regulation play important roles in various cellular functions. The regulation of peroxisomal metabolism is controlled by modulation of peroxisome biogenesis as well as the degradation of intra-organellar components and the organelle itself. An accumulation of experimental findings demonstrate that the majority of organelle degradation is accomplished through autophagy, an important cellular process involving transport of cytoplasmic constituents into lysosomes for degradation. The first part of this chapter discusses several processes responsible for the degradation of peroxisomes in mammalian cells, including autophagy. Next, following a general description of the molecular machinery of autophagy, molecular details of selective autophagy of peroxisomes, termed pexophagy, are described based on studies conducted in yeast and mammalian cells. In the final section, expected medical applications associated with pexophagy are described along with potential future developments in this field.
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References
Aksam EB et al (2007) A peroxisomal lon protease and peroxisome degradation by autophagy play key roles in vitality of Hansenula polymorpha cells. Autophagy 3:96–105
Colakoglu M, Tuncer S, Banerjee S (2018) Emerging cellular functions of the lipid metabolizing enzyme 15-lipoxygenase-1. Cell Prolif 51:e12472
Deosaran E et al (2013) NBR1 acts as an autophagy receptor for peroxisomes. J Cell Sci 126:939–952
Farre JC et al (2008) PpAtg30 tags peroxisomes for turnover by selective autophagy. Dev Cell 14:365–376
Farre JC et al (2013) Phosphorylation of mitophagy and pexophagy receptors coordinates their interaction with Atg8 and Atg11. EMBO Rep 14:441–449
Hanada T et al (2007) The Atg12-Atg5 conjugate has a novel E3-like activity for protein lipidation in autophagy. J Biol Chem 282:37298–37302
Hara-Kuge S, Fujiki Y (2008) The peroxin Pex14p is involved in LC3-dependent degradation of mammalian peroxisomes. Exp Cell Res 314:3531–3541
Huybrechts SJ et al (2009) Peroxisome dynamics in cultured mammalian cells. Traffic 10:1722–1733
Ichimura Y et al (2000) A ubiquitin-like system mediates protein lipidation. Nature 408:488–492
Iijima K et al (2008) Dancing on damaged chromatin: functions of ATM and the RAD50/MRE11/NBS1 complex in cellular responses to DNA damage. J Radiat Res 49:451–464
Imai K et al (2016) Atg9A trafficking through the recycling endosomes is required for autophagosome formation. J Cell Sci 129:3781
Iwata J et al (2006) Excess peroxisomes are degraded by autophagic machinery in mammals. J Biol Chem 281:4035–4041
Jiang L et al (2015) Peroxin Pex14p is the key component for coordinated autophagic degradation of mammalian peroxisomes by direct binding to LC3-II. Genes Cells 20:36–49
Kabeya Y et al (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728
Keith B, Johnson RS, Simon MC (2011) HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer 12:9–22
Kihara A et al (2001) Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J Cell Biol 152:519–530
Kikuchi M et al (2004) Proteomic analysis of rat liver peroxisome: presence of peroxisome-specific isozyme of Lon protease. J Biol Chem 279:421–428
Kim PK et al (2008) Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci U S A 105:20567–20574
Kirkin V et al (2009) A role for ubiquitin in selective autophagy. Mol Cell 34:259–269
Klionsky DJ et al (2003) A unified nomenclature for yeast autophagy-related genes. Dev Cell 5:539–545
Lamark T et al (2003) Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins. J Biol Chem 278:34568–34581
Law KB et al (2017) The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders. Autophagy 13:868–884
Lee JN et al (2018) Catalase inhibition induces pexophagy through ROS accumulation. Biochem Biophys Res Commun 501:696–702
Luiken JJ et al (1992) Autophagic degradation of peroxisomes in isolated rat hepatocytes. FEBS Lett 304:93–97
Marcassa E et al (2018) Dual role of USP30 in controlling basal pexophagy and mitophagy. EMBO Rep 19:e45595
Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741
Mizushima N et al (1998) A protein conjugation system essential for autophagy. Nature 395:395–398
Motley AM, Nuttall JM, Hettema EH (2012) Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae. EMBO J 31:2852–2868
Mukaiyama H et al (2002) Paz2 and 13 other PAZ gene products regulate vacuolar engulfment of peroxisomes during micropexophagy. Genes Cells 7:75–90
Mukaiyama H et al (2004) Modification of a ubiquitin-like protein Paz2 conducted micropexophagy through formation of a novel membrane structure. Mol Biol Cell 15:58–70
Nazarko TY et al (2014) Peroxisomal Atg37 binds Atg30 or palmitoyl-CoA to regulate phagophore formation during pexophagy. J Cell Biol 204:541–557
Noda NN, Ohsumi Y, Inagaki F (2010) Atg8-family interacting motif crucial for selective autophagy. FEBS Lett 584:1379–1385
Nordgren M et al (2015) Export-deficient monoubiquitinated PEX5 triggers peroxisome removal in SV40 large T antigen-transformed mouse embryonic fibroblasts. Autophagy 11:1326–1340
Nuttall JM, Motley AM, Hettema EH (2014) Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae. Autophagy 10:835–845
Obara K et al (2008) The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J Biol Chem 283:23972–23980
Papinski D, Kraft C (2016) Regulation of autophagy by signaling through the Atg1/ULK1 complex. J Mol Biol 428:1725–1741
Pomatto LC, Raynes R, Davies KJ (2017) The peroxisomal Lon protease LonP2 in aging and disease: functions and comparisons with mitochondrial Lon protease LonP1. Biol Rev Camb Philos Soc 92:739–753
Reddy JK et al (1982) Hepatic and renal effects of peroxisome proliferators: biological implications. Ann N Y Acad Sci 386:81–110
Riccio V et al (2019) Deubiquitinating enzyme USP30 maintains basal peroxisome abundance by regulating pexophagy. J Cell Biol 218:798–807
Sargent G et al (2016) PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation. J Cell Biol 214:677–690
Schittek B, Sinnberg T (2014) Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis. Mol Cancer 13:231
Seglen PO, Gordon PB (1982) 3-methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc Natl Acad Sci U S A 79:1889–1892
Shintani T et al (1999) Apg10p, a novel protein-conjugating enzyme essential for autophagy in yeast. EMBO J 18:5234–5241
Suzuki H et al (2017) Structural biology of the core autophagy machinery. Curr Opin Struct Biol 43:10–17
Tanaka C et al (2014) Hrr25 triggers selective autophagy-related pathways by phosphorylating receptor proteins. J Cell Biol 207:91–105
Titorenko VI et al (1995) Isolation and characterization of mutants impaired in the selective degradation of peroxisomes in the yeast Hansenula polymorpha. J Bacteriol 177:357–363
Tsukada M, Ohsumi Y (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 333:169–174
Tuttle DL, Dunn WA Jr (1995) Divergent modes of autophagy in the methylotrophic yeast Pichia pastoris. J Cell Sci 108:25–35
van Leyen K et al (1998) A function for lipoxygenase in programmed organelle degradation. Nature 395:392–395
Veenhuis M et al (1983) Degradation and turnover of peroxisomes in the yeast Hansenula polymorpha induced by selective inactivation of peroxisomal enzymes. Arch Microbiol 134:193–203
Walter KM et al (2014) Hif-2alpha promotes degradation of mammalian peroxisomes by selective autophagy. Cell Metab 20:882–897
Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9:1102–1109
Yamamoto H et al (2012) Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol 198:219
Yamashita S et al (2014) The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy. Autophagy 10:1549–1564
Yokota S (1993) Formation of autophagosomes during degradation of excess peroxisomes induced by administration of dioctyl phthalate. Eur J Cell Biol 61:67–80
Yokota S, Dariush Fahimi H (2009) Degradation of excess peroxisomes in mammalian liver cells by autophagy and other mechanisms. Histochem Cell Biol 131:455–458
Yokota S et al (1993) Formation of autophagosomes during degradation of excess peroxisomes induced by di-(2-ethylhexyl)phthalate treatment. II. Immunocytochemical analysis of early and late autophagosomes. Eur J Cell Biol 62:372–383
Yokota S, Oda T, Fahimi HD (2001) The role of 15-lipoxygenase in disruption of the peroxisomal membrane and in programmed degradation of peroxisomes in normal rat liver. J Histochem Cytochem 49:613–622
Yokota S, Haraguchi CM, Oda T (2008) Induction of peroxisomal Lon protease in rat liver after di-(2-ethylhexyl)phthalate treatment. Histochem Cell Biol 129:73–83
Zhang J et al (2015) ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat Cell Biol 17:1259–1269
Zientara-Rytter K et al (2018) Pex3 and Atg37 compete to regulate the interaction between the pexophagy receptor, Atg30, and the Hrr25 kinase. Autophagy 14:368–384
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Oku, M., Sakai, Y. (2019). Peroxisome Degradation and Its Molecular Machinery. In: Imanaka, T., Shimozawa, N. (eds) Peroxisomes: Biogenesis, Function, and Role in Human Disease. Springer, Singapore. https://doi.org/10.1007/978-981-15-1169-1_3
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DOI: https://doi.org/10.1007/978-981-15-1169-1_3
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