Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Pexophagy: Molecular Mechanisms and Implications for Health and Diseases

  • Cho, Dong-Hyung (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Yi Sak (Department of Microbiology, Chungnam National University School of Medicine) ;
  • Jo, Doo Sin (Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Choe, Seong-Kyu (Department of Microbiology and Center for Metabolic Function Regulation, Wonkwang University School of Medicine) ;
  • Jo, Eun-Kyeong (Department of Microbiology, Chungnam National University School of Medicine)
  • Received : 2017.10.18
  • Accepted : 2017.12.29
  • Published : 2018.01.31
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Abstract

Autophagy is an intracellular degradation pathway for large protein aggregates and damaged organelles. Recent studies have indicated that autophagy targets cargoes through a selective degradation pathway called selective autophagy. Peroxisomes are dynamic organelles that are crucial for health and development. Pexophagy is selective autophagy that targets peroxisomes and is essential for the maintenance of homeostasis of peroxisomes, which is necessary in the prevention of various peroxisome-related disorders. However, the mechanisms by which pexophagy is regulated and the key players that induce and modulate pexophagy are largely unknown. In this review, we focus on our current understanding of how pexophagy is induced and regulated, and the selective adaptors involved in mediating pexophagy. Furthermore, we discuss current findings on the roles of pexophagy in physiological and pathological responses, which provide insight into the clinical relevance of pexophagy regulation. Understanding how pexophagy interacts with various biological functions will provide fundamental insights into the function of pexophagy and facilitate the development of novel therapeutics against peroxisomal dysfunction-related diseases.

Keywords

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Fig. 1. A model of peroxisomal biogenesis. Peroxisome biogenesis is coordinated by two different pathways, de novo biogenesis and the ‘growth and division’. First, peroxisomes can be formed by peroxisome assembly and maturation of pre-peroxisomal vesicles originated from ER or mitochondria, which contain preperoxisomal carriers, including PEX3 and PEX16. Second, peroxisomes can proliferate the numbers by a growth and division progress from existing peroxisomes. PEX11 and Drp1 proteins mediate elongation and fission of the peroxisomes.

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Fig. 2. Pexophagy regulators. Pexophagy istriggered by both stress conditions andperoxisomal dysfunctions. Ubiquitination ofPMPs, such as peroxins and PMP70, pro-motes pexophagy. Both NBR1 and p62 actas autophagy adaptor proteins, which in-teract with PMPs and sequester target pe-roxisome into autophagosomes. Underconditions of oxidative stress, the ataxia-telangiectasia mutation activates pexopha-gy by phosphorylating PEX5, leading to itsubiquitination. Pexophagy may be regulat-ed by an unidentified protein (X).

Table 1. Peroxisomal proteins and their relevance with pathological aspects

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References

  1. Al-Dirbashi, O.Y., Shaheen, R., Al-Sayed, M., Al-Dosari, M., Makhseed, N., Abu Safieh, L., Santa, T., Meyer, B.F., Shimozawa, N., and Alkuraya, F.S. (2009). Zellweger syndrome caused by PEX13 deficiency: report of two novel mutations. Am. J. Med. Genet. A 149A, 1219-1223. https://doi.org/10.1002/ajmg.a.32874
  2. Anding, A.L., and Baehrecke, E.H. (2017). Cleaning House: Selective Autophagy of Organelles. Dev. Cell 41, 10-22. https://doi.org/10.1016/j.devcel.2017.02.016
  3. Baroy, T., Koster, J., Stromme, P., Ebberink, M.S., Misceo, D., Ferdinandusse, S., Holmgren, A., Hughes, T., Merckoll, E., Westvik, J., et al. (2015). A novel type of rhizomelic chondrodysplasia punctata, RCDP5, is caused by loss of the PEX5 long isoform. Hum. Mol. Genet. 24, 5845-5854. https://doi.org/10.1093/hmg/ddv305
  4. Bjorkoy, G., Lamark, T., Brech, A., Outzen, H., Perander, M., Overvatn, A., Stenmark, H., and Johansen, T. (2005). p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J. Cell Biol. 171, 603-614. https://doi.org/10.1083/jcb.200507002
  5. Bonekamp,N.A., Volkl,A., Fahimi, H.D., and Schrader, M. (2009). Reactive oxygen species and peroxisomes: struggling for balance. Biofactors 35, 346-355. https://doi.org/10.1002/biof.48
  6. Bowers, W.E. (1998). Christian de Duve and the discovery of lysosomes and peroxisomes. Trends Cell Biol 8, 330-333. https://doi.org/10.1016/S0962-8924(98)01314-2
  7. Braverman, N., Steel, G., Obie, C., Moser, A., Moser, H., Gould, S.J., and Valle, D. (1997). Human PEX7 encodes the peroxisomal PTS2 receptor and is responsible for rhizomelic chondrodysplasia punctata. Nat. Genet. 15, 369-376. https://doi.org/10.1038/ng0497-369
  8. Braverman, N.E., D'Agostino, M.D., and Maclean, G.E. (2013). Peroxisome biogenesis disorders: Biological, clinical and pathophysiological perspectives. Dev. Disabil Res. Rev. 17, 187-196. https://doi.org/10.1002/ddrr.1113
  9. Campbell, I.G., Nicolai, H.M., Foulkes, W.D., Senger, G., Stamp, G.W., Allan, G., Boyer, C., Jones, K., Bast, R.C. Jr., and Solomon, E. (1994). A novel gene encoding a B-box protein within the BRCA1 region at 17q21.1. Hum. Mol. Genet. 3, 589-594. https://doi.org/10.1093/hmg/3.4.589
  10. Chang, C.C., Lee, W.H., Moser, H., Valle, D., and Gould, S.J. (1997). Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders. Nat. Genet. 15, 385-388. https://doi.org/10.1038/ng0497-385
  11. Choi, M., Kipps, T., and Kurzrock, R. (2016). ATM mutations in cancer: therapeutic implications. Mol. Cancer Ther. 15, 1781-1791. https://doi.org/10.1158/1535-7163.MCT-15-0945
  12. Choy, K.R., and Watters, D.J. (2017). Neurodegeneration in ataxiatelangiectasia: Multiple roles of ATM kinase in cellular homeostasis. Dev Dyn, 2017 May 2022. doi: 2010.1002/dvdy.24522.
  13. Deb, R., and Nagotu, S. (2017). Versatility of peroxisomes: An evolving concept. Tissue Cell 49, 209-226. https://doi.org/10.1016/j.tice.2017.03.002
  14. Demarquoy, J., and Le Borgne, F. (2015). Crosstalk between mitochondria and peroxisomes. World J. Biol. Chem. 26, 301-309.
  15. Deosaran, E., Larsen, K.B., Hua, R., Sargent, G., Wang, Y., Kim, S., Lamark, T., Jauregui, M., Law, K., Lippincott-Schwartz, J., et al. (2013). NBR1 acts as an autophagy receptor for peroxisomes. J. Cell Sci. 126, 939-952. https://doi.org/10.1242/jcs.114819
  16. Dirkx, R., Vanhorebeek, I., Martens, K., Schad, A., Grabenbauer, M., Fahimi, D., Declercq, P., Van Veldhoven, P.P., and Baes, M. (2005). Absence of peroxisomes in mouse hepatocytes causes mitochondrial and ER abnormalities. Hepatology 41, 868-878. https://doi.org/10.1002/hep.20628
  17. Du, H., Kim, S., Hur, Y.S., Lee, M.S., Lee, S.H. and Cheon, C.I. (2015). A cytosolic thioredoxin acts as a molecular chaperone for peroxisome matrix proteins as well as antioxidant in peroxisome. Mol. Cells 38, 187-194. https://doi.org/10.14348/molcells.2015.2255
  18. Duran, A., Linares, J.F., Galvez, A.S., Wikenheiser, K., Flores, J.M., Diaz-Meco, M.T., and Moscat, J. (2008). The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 13, 343-354. https://doi.org/10.1016/j.ccr.2008.02.001
  19. Ebberink, M.S., Koster, J., Visser, G., Spronsen, Fv., Stolte-Dijkstra, I., Smit, G.P., Fock, J.M., Kemp, S., Wanders, R.J., and Waterham, H.R. (2012). A novel defect of peroxisome division due to a homozygous non-sense mutation in the PEX11beta gene. J. Med. Genet. 49, 307-313. https://doi.org/10.1136/jmedgenet-2012-100778
  20. Feng, L., Zhang, J., Zhu, N., Ding, Q., Zhang, X., Yu, J., Qiang, W., Zhang, Z., Ma, Y., Huang, D., et al. (2017). Ubiquitin ligase SYVN1/HRD1 facilitates degradation of the SERPINA1 Z variant/alpha-1-antitrypsin Z variant via SQSTM1/p62-dependent selective autophagy. Autophagy 13, 686-702. https://doi.org/10.1080/15548627.2017.1280207
  21. Ferdinandusse, S., Falkenberg, K.D., Koster, J., Mooyer, P.A., Jones, R., van Roermund, C.W.T., Pizzino, A., Schrader, M., Wanders, R.J.A., Vanderver, A., et al. (2017). ACBD5 deficiency causes a defect in peroxisomal very long-chain fatty acid metabolism. J. Med. Genet. 54, 330-337. https://doi.org/10.1136/jmedgenet-2016-104132
  22. Fransen, M., Nordgren, M., Wang, B., and Apanasets, O. (2012). Role of peroxisomes in ROS/RNS-metabolism: implications for human disease. Biochim. Biophys. Acta 1822, 1363-1373. https://doi.org/10.1016/j.bbadis.2011.12.001
  23. Gao, X., and Schottker, B. (2017). Reduction-oxidation pathways involved in cancer development: a systematic review of literature reviews. Oncotarget 8, 51888-51906.
  24. Giannopoulou, E.A., Emmanouilidis, L., Sattler, M., Dodt, G., and Wilmanns, M. (2016). Towards the molecular mechanism of the integration of peroxisomal membrane proteins. Biochim. Biophys. Acta 1863, 863-869. https://doi.org/10.1016/j.bbamcr.2015.09.031
  25. Goldfischer, S., Moore, C.L., Johnson, A.B., Spiro, A.J., Valsamis, M.P., Wisniewski, H.K., Ritch, R.H., Norton, W.T., Rapin, I., and Gartner, L.M. (1973). Peroxisomal and mitochondrial defects in the cerebrohepato-renal syndrome. Science 182, 62-64. https://doi.org/10.1126/science.182.4107.62
  26. Gould, S.J., and Valle D. (2000). Peroxisome biogenesis disorders: genetics and cell biology. Trends Genet. 16, 340-345. https://doi.org/10.1016/S0168-9525(00)02056-4
  27. Heiland, I., and Erdmann, R. (2005). Biogenesis of peroxisomes. Topogenesis of the peroxisomal membrane and matrix proteins. FEBS J. 272, 2362-2372. https://doi.org/10.1111/j.1742-4658.2005.04690.x
  28. Heymans, H.S., Schutgens, R.B., Tan, R., van den Bosch, H., and Borst, P. (1983). Severe plasmalogen deficiency in tissues of infants without peroxisomes (Zellweger syndrome). Nature 306, 69-70. https://doi.org/10.1038/306069a0
  29. Heymans, H.S., Oorthuys, J.W., Nelck, G., Wanders, R.J., and Schutgens, R.B. (1985). Rhizomelic chondrodysplasia punctata: another peroxisomal disorder. N Engl. J. Med. 313, 187-188.
  30. Hiltunen, J.K., Mursula, A.M., Rottensteiner, H., Wierenga, R.K., Kastaniotis, A.J., Gurvitz, A. (2003). The biochemistry of peroxisomal beta-oxidation in the yeast Saccharomyces cerevisiae. FEMS Microbiol. Rev. 27, 35-64. https://doi.org/10.1016/S0168-6445(03)00017-2
  31. Honsho, M., Yamashita, S., and Fujiki, Y. (2016). Peroxisome homeostasis: Mechanisms of division and selective degradation of peroxisomes in mammals. Biochim. Biophys. Acta 1863, 984-991. https://doi.org/10.1016/j.bbamcr.2015.09.032
  32. Hu, J., Baker, A., Bartel, B., Linka, N., Mullen, R.T., Reumann, S., and Zolman, B.K. (2012). Plant peroxisomes: biogenesis and function. Plant Cell 24, 2279-2303. https://doi.org/10.1105/tpc.112.096586
  33. Hua, R., and Kim, P.K. (2016). Multiple paths to peroxisomes: Mechanism of peroxisome maintenance in mammals. Biochim Biophys Acta 1863, 881-891. https://doi.org/10.1016/j.bbamcr.2015.09.026
  34. Huybrechts, S.J., Van Veldhoven, P.P., Hoffman, I., Zeevaert, R., de Vos, R., Demaerel, P., Brams, M., Jaeken, J., Fransen, M., and Cassiman, D. (2008). Identification of a novel PEX14 mutation in Zellweger syndrome. J. Med. Genet. 45, 376-383. https://doi.org/10.1136/jmg.2007.056697
  35. Huybrechts, S.J., Van Veldhoven, P.P., Brees, C., Mannaerts, G.P., Los, G.V., and Fransen, M. (2009). Peroxisome dynamics in cultured mammalian cells. Traffic 10, 1722-1733. https://doi.org/10.1111/j.1600-0854.2009.00970.x
  36. Ichimura, Y., Kumanomidou, T., Sou, Y.S., Mizushima, T., Ezaki, J., Ueno, T., Kominami, E., Yamane, T., Tanaka, K., and Komatsu, M. (2008). Structural basis for sorting mechanism of p62 in selective autophagy. J. Biol. Chem. 283, 22847-22857. https://doi.org/10.1074/jbc.M802182200
  37. Islinger, M., Cardoso, M.J., and Schrader, M. (2010). Be different--the diversity of peroxisomes in the animal kingdom. Biochim. Biophys. Acta 1803, 881-897. https://doi.org/10.1016/j.bbamcr.2010.03.013
  38. Jain, A., Lamark, T., Sjottem, E., Larsen, K.B., Awuh, J.A., Overvatn, A., McMahon, M., Hayes, J.D., and Johansen, T. (2010). p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J. Biol. Chem. 285, 22576-22591. https://doi.org/10.1074/jbc.M110.118976
  39. Jiang, L., Hara-Kuge, S., Yamashita, S. and Fujiki, Y. (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. https://doi.org/10.1111/gtc.12198
  40. Johansen, T., and Lamark, T. (2011). Selective autophagy mediated by autophagic adapter proteins. Autophagy 7, 279-296. https://doi.org/10.4161/auto.7.3.14487
  41. Katsuragi, Y., Ichimura, Y., and Komatsu, M. (2015). p62/SQSTM1 functions as a signaling hub and an autophagy adaptor. FEBS J. 282, 4672-4678. https://doi.org/10.1111/febs.13540
  42. Kiel, J.A., Veenhuis, M., van der Klei, I.J. (2006). PEX genes in fungal genomes: common, rare or redundant. Traffic 7, 1291-1303. https://doi.org/10.1111/j.1600-0854.2006.00479.x
  43. Kim, P.K. (2017). Peroxisome biogenesis: a union between two organelles. Curr. Biol. 27, R271-R274. https://doi.org/10.1016/j.cub.2017.02.052
  44. Kim, Y.C., and Guan, K.L. (2015). mTOR: a pharmacologic target for autophagy regulation. J. Clin. Invest 125, 25-32. https://doi.org/10.1172/JCI73939
  45. Kim, P.K., Hailey, D.W., Mullen, R.T., and Lippincott-Schwartz, J. (2008). Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc. Natl. Acad. Sci. USA 105, 20567-20574. https://doi.org/10.1073/pnas.0810611105
  46. Kim, Y.S., Lee, H.M., Kim, J.K., Yang, C.S., Kim, T.S., Jung, M., Jin, H.S., Kim, S., Jang, J., Oh, G.T., et al. (2017). $PPAR-{\alpha}$ activation mediates innate host defense through induction of TFEB and lipid catabolism. J. Immunol. 198, 3283-3295. https://doi.org/10.4049/jimmunol.1601920
  47. Kirkin, V., Lamark, T., Sou, Y.S., Bjorkoy, G., Nunn, J.L., Bruun, J.A., Shvets, E., McEwan, D.G., Clausen, T.H., Wild, P., et al. (2009). A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol. Cell 33, 505-516. https://doi.org/10.1016/j.molcel.2009.01.020
  48. Klionsky, D.J., Abdelmohsen, K., Abe, A., Abedin, M.J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C.M., Adams, P.D., Adeli, K., et al. ( 2016). Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy 12, 1-222. https://doi.org/10.1080/15548627.2015.1100356
  49. Komatsu, M., Waguri, S., Koike, M., Sou, Y.S., Ueno, T., Hara, T., Mizushima, N., Iwata, J., Ezaki, J., Murata, S., et al. (2007). Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149-1163. https://doi.org/10.1016/j.cell.2007.10.035
  50. Kumar, S., Kawalek, A., and van der Klei, I.J. (2014). Peroxisomal quality control mechanisms. Curr. Opin. Microbiol. 22, 30-37. https://doi.org/10.1016/j.mib.2014.09.009
  51. Law, K.B., Bronte-Tinkew, D., Di Pietro, E., Snowden, A., Jones, R.O., Moser, A., Brumell, J.H., Braverman, N., and Kim, P.K. (2017). The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders. Autophagy 13, 868-884. https://doi.org/10.1080/15548627.2017.1291470
  52. Lazarou, M., Sliter, D.A., Kane, L.A., Sarraf, S.A., Wang, C., Burman, J.L., Sideris, D.P., Fogel, A.I. and Youle, R.J. (2015). The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature 524, 309-314. https://doi.org/10.1038/nature14893
  53. Lee, J.M., Wagner, M., Xiao, R., Kim, K.H., Feng, D., Lazar, M.A., and Moore, D.D. (2014). Nutrient-sensing nuclear receptors coordinate autophagy. Nature 516, 112-115.
  54. Lee, M.Y., Sumpter, R., Jr., Zou, Z., Sirasanagandla, S., Wei, Y., Mishra, P., Rosewich, H., Crane, D.I. and Levine, B. (2017). Peroxisomal protein PEX13 functions in selective autophagy. EMBO Rep. 18, 48-60. https://doi.org/10.15252/embr.201642443
  55. Linares. J.F., Duran, A., Yajima, T., Pasparakis, M., Moscat, J., and Diaz-Meco, M.T. (2013). K63 polyubiquitination and activation of mTOR by the p62-TRAF6 complex in nutrient-activated cells. Mol. Cell 51, 283-296. https://doi.org/10.1016/j.molcel.2013.06.020
  56. Liu, Y., Bjorkman, J., Urquhart, A., Wanders, R.J., Crane, D.I., and Gould, S.J. (1999). PEX13 is mutated in complementation group 13 of the peroxisome-biogenesis disorders. Am. J. Hum. Genet. 65, 621-634. https://doi.org/10.1086/302534
  57. Liu, X.F., Hao, J.L., Xie, T., Malik, T.H., Lu, C.B., Liu, C., Shu, C., Lu, C.W., and Zhou, D.D. (2017). Nrf2 as a target for prevention of agerelated and diabetic cataracts by against oxidative stress. Aging Cell 16, 934-942. https://doi.org/10.1111/acel.12645
  58. Mardakheh, F.K., Auciello, G., Dafforn, T.R., Rappoport, J.Z., and Heath, J.K. (2010). Nbr1 is a novel inhibitor of ligand-mediated receptor tyrosine kinase degradation. Mol. Cell Biol. 30, 5672-5685. https://doi.org/10.1128/MCB.00878-10
  59. Martinez-Vicente, M. (2017). Neuronal mitophagy in neurodegenerative diseases. Front Mol. Neurosci. 10, 64.
  60. Mathew, R., Karp, C.M., Beaudoin, B., Vuong, N., Chen, G., Chen, H.Y., Bray, K., Reddy, A., Bhanot, G., Gelinas, C., et al. (2009). Autophagy suppresses tumorigenesis through elimination of p62. Cell 137, 1062-1075. https://doi.org/10.1016/j.cell.2009.03.048
  61. Matsumoto, N., Tamura, S., Furuki, S., Miyata, N., Moser, A., Shimozawa, N., Moser, H.W., Suzuki, Y., Kondo, N., and Fujiki, Y. (2003). Mutations in novel peroxin gene PEX26 that cause peroxisome-biogenesis disorders of complementation group 8 provide a genotype-phenotype correlation. Am. J. Hum. Genet. 73, 233-246. https://doi.org/10.1086/377004
  62. Matsuzono, Y., Kinoshita, N., Tamura, S., Shimozawa, N., Hamasaki, M., Ghaedi, K., Wanders, R.J., Suzuki, Y., Kondo, N., and Fujiki, Y. (1999). Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly. Proc. Natl. Acad. Sci. USA 96, 2116-2121. https://doi.org/10.1073/pnas.96.5.2116
  63. Mayerhofer, P.U. (2016). Targeting and insertion of peroxisomal membrane proteins: ER trafficking versus direct delivery to peroxisomes. Biochim. Biophys. Acta 1863, 870-880. https://doi.org/10.1016/j.bbamcr.2015.09.021
  64. Moser, A.E., Singh, I., Brown, F.R. 3rd., Solish, G.I., Kelley, R.I., Benke, P.J., Moser, H.W. (1984). The cerebrohepatorenal (Zellweger) syndrome. Increased levels and impaired degradation of very-longchain fatty acids and their use in prenatal diagnosis. N Engl J Med 310, 1141-1146. https://doi.org/10.1056/NEJM198405033101802
  65. Muntau, A.C., Mayerhofer, P.U., Paton, B.C., Kammerer, S., and Roscher, A.A. (2000). Defective peroxisome membrane synthesis due to mutations in human PEX3 causes Zellweger syndrome, complementation group G. Am. J. Hum. Genet. 67, 967-975. https://doi.org/10.1086/303071
  66. Nazarko, T.Y. (2014). Atg37 regulates the assembly of the pexophagic receptor protein complex. Autophagy 10, 1348-1349. https://doi.org/10.4161/auto.29073
  67. Nazarko, T.Y. (2017). Pexophagy is responsible for 65% of cases of peroxisome biogenesis disorders. Autophagy 13, 991-994. https://doi.org/10.1080/15548627.2017.1291480
  68. Nordgren, M., Francisco, T., Lismont, C., Hennebel, L., Brees, C., Wang, B., Van Veldhoven, P.P., Azevedo, J.E., and Fransen, M. (2015). Export-deficient monoubiquitinated PEX5 triggers peroxisome removal in SV40 large T antigen-transformed mouse embryonic fibroblasts. Autophagy 11, 1326-1340. https://doi.org/10.1080/15548627.2015.1061846
  69. Pawlak, M., Lefebvre, P., and Staels, B. (2015). Molecular mechanism of $PPAR{\alpha}$ action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. J. Hepatol. 62, 720-733 https://doi.org/10.1016/j.jhep.2014.10.039
  70. Platta, H.W., Hagen, S., Reidick, C., and Erdmann, R. (2014). The peroxisomal receptor dislocation pathway: to the exportomer and beyond. Biochimie 98, 16-28. https://doi.org/10.1016/j.biochi.2013.12.009
  71. Poirier, Y., Antonenkov, V.D., Glumoff, T., and Hiltunen, J.K. (2006). Peroxisomal beta-oxidation--a metabolic pathway with multiple functions. Biochim. Biophys. Acta 1763, 1413-1426 https://doi.org/10.1016/j.bbamcr.2006.08.034
  72. Rakhshandehroo, M., Hooiveld, G., Muller, M., and Kersten, S. (2009). Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human. PLoS One 4, e6796. https://doi.org/10.1371/journal.pone.0006796
  73. Reuber, B.E., Germain-Lee, E., Collins, C.S., Morrell, J.C., Ameritunga, R., Moser, H.W., Valle, D., and Gould, S.J. (1997). Mutations in PEX1 are the most common cause of peroxisome biogenesis disorders. Nat. Genet. 17, 445-448. https://doi.org/10.1038/ng1297-445
  74. Ryter, S.W., Cloonan, S.M. and Choi, A.M. (2013). Autophagy: a critical regulator of cellular metabolism and homeostasis. Mol. Cells 36, 7-16. https://doi.org/10.1007/s10059-013-0140-8
  75. Sargent, G., van Zutphen, T., Shatseva, T., Zhang, L., Di Giovanni, V., Bandsma, R. and Kim, P.K. (2016). PEX2 is the E3 ubiquitin ligase required for pexophagy during starvation. J. Cell Biol. 214, 677-690. https://doi.org/10.1083/jcb.201511034
  76. Schluter, A., Fourcade, S., Ripp, R., Mandel, J.L., Poch, O., and Pujol, A. (2006). The evolutionary origin of peroxisomes: an ER-peroxisome connection. Mol. Biol. Evol. 23, 838-845. https://doi.org/10.1093/molbev/msj103
  77. Shimozawa, N., Imamura, A., Zhang, Z., Suzuki, Y., Orii, T., Tsukamoto, T., Osumi, T., Fujiki, Y., Wanders, R.J., Besley, G., et al. (1999a). Defective PEX gene products correlate with the protein import, biochemical abnormalities, and phenotypic heterogeneity in peroxisome biogenesis disorders. J. Med. Genet. 36, 779-781. https://doi.org/10.1136/jmg.36.10.779
  78. Shimozawa, N., Suzuki, Y., Zhang, Z., Imamura, A., Toyama, R., Mukai, S., Fujiki, Y., Tsukamoto, T., Osumi, T., Orii, T., et al. (1999b). Nonsense and temperature-sensitive mutations in PEX13 are the cause of complementation group H of peroxisome biogenesis disorders. Hum. Mol. Genet. 8, 1077-1083. https://doi.org/10.1093/hmg/8.6.1077
  79. Shimozawa, N., Zhang, Z., Suzuki, Y., Imamura, A., Tsukamoto, T., Osumi, T., Fujiki, Y., Orii, T., Barth, P.G., Wanders, R.J., et al. (1999c). Functional heterogeneity of C-terminal peroxisome targeting signal 1 in PEX5-defective patients. Biochem. Biophys. Res. Commun. 262, 504-508. https://doi.org/10.1006/bbrc.1999.1232
  80. Smith, C.E., Poulter, J.A., Levin, A.V., Capasso, J.E., Price, S., Ben-Yosef, T., Sharony, R., Newman, W.G., Shore, R.C., Brookes, S.J., et al. (2016). Spectrum of PEX1 and PEX6 variants in Heimler syndrome. Eur. J. Hum. Genet. 24, 1565-1571. https://doi.org/10.1038/ejhg.2016.62
  81. South, S.T., and Gould, S.J. (1999). Peroxisome synthesis in the absence of preexisting peroxisomes. J Cell Biol 144, 255-266. https://doi.org/10.1083/jcb.144.2.255
  82. Tamura, S., Matsumoto, N., Imamura, A., Shimozawa, N., Suzuki, Y., Kondo, N., and Fujiki, Y. (2001). Phenotype-genotype relationships in peroxisome biogenesis disorders of PEX1-defective complementation group 1 are defined by Pex1p-Pex6p interaction. Biochem. J. 357, 417-426.
  83. Tumbarello, D.A., Manna, P.T., Allen, M., Bycroft, M., Arden, S.D., Kendrick-Jones, J. and Buss, F. (2015). The autophagy receptor TAX1BP1 and the molecular motor myosin VI are required for clearance of salmonella typhimurium by autophagy. PLoS Pathog. 11, e1005174. https://doi.org/10.1371/journal.ppat.1005174
  84. Vadlamudi, R.K., Joung, I., Strominger, J.L., and Shin, J. (1996). p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins. J Biol Chem 271, 20235-20237. https://doi.org/10.1074/jbc.271.34.20235
  85. Van den Brink, D.M., Brites, P., Haasjes, J., Wierzbicki, A.S., Mitchell, J., Lambert-Hamill, M., de Belleroche, J., Jansen, G.A., Waterham, H.R., and Wanders, R.J. (2003). Identification of PEX7 as the second gene involved in Refsum disease. Am. J. Hum. Genet. 72, 471-477. https://doi.org/10.1086/346093
  86. Van Os, N.J., Roeleveld, N., Weemaes, C.M., Jongmans, M.C., Janssens, G.O., Taylor, A.M., Hoogerbrugge, N., and Willemsen, M.A. (2016). Health risks for ataxia-telangiectasia mutated heterozygotes: a systematic review, meta-analysis and evidence-based guideline. Clin. Genet. 90, 105-117. https://doi.org/10.1111/cge.12710
  87. Vasko, R., Ratliff, B.B., Bohr, S., Nadel, E., Chen, J., Xavier, S., Chander, P., and Goligorsky, M.S. (2013). Endothelial peroxisomal dysfunction and impaired pexophagy promotes oxidative damage in lipopolysaccharide-induced acute kidney injury. Antioxid. Redox. Signal. 19, 211-230. https://doi.org/10.1089/ars.2012.4768
  88. Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R.L., Kim, J., May, J., Tocilescu, M.A., Liu, W., Ko, H.S., et al. (2010). PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A 107, 378-383. https://doi.org/10.1073/pnas.0911187107
  89. Von Muhlinen, N., Thurston, T., Ryzhakov, G., Bloor, S. and Randow, F. (2010.) NDP52, a novel autophagy receptor for ubiquitin-decorated cytosolic bacteria. Autophagy 6, 288-289. https://doi.org/10.4161/auto.6.2.11118
  90. Wanders, R.J., Waterham, H.R., and Ferdinandusse, S. (2016). Metabolic Interplay between peroxisomes and other subcellular organelles including mitochondria and the endoplasmic reticulum. Front Cell Dev. Biol. 3, 83.
  91. Wanders, R.J., Klouwer, F.C., Ferdinandusse, S., Waterham, H.R., and Poll-The, B.T. (2017). clinical and laboratory diagnosis of peroxisomal disorders. Methods Mol. Biol. 1595, 329-342.
  92. Warren, D.S., Morrell, J.C., Moser, H.W., Valle, D., and Gould, S.J. (1998). Identification of PEX10, the gene defective in complementation group 7 of the peroxisome-biogenesis disorders. Am. J. Hum. Genet. 63, 347-359. https://doi.org/10.1086/301963
  93. Waterham, H.R., Ferdinandusse, S., and Wanders, R.J. (2016). Human disorders of peroxisome metabolism and biogenesis. Biochim. Biophys. Acta 1863, 922-933. https://doi.org/10.1016/j.bbamcr.2015.11.015
  94. Wong, Y.C. and Holzbaur, E.L. (2014). Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc. Natl. Acad. Sci. USA 111, E4439-4448. https://doi.org/10.1073/pnas.1405752111
  95. Yamashita, S., Abe, K., Tatemichi, Y., and Fujiki, Y. (2014). The membrane peroxin PEX3 induces peroxisome-ubiquitination-linked pexophagy. Autophagy 10, 1549-1564. https://doi.org/10.4161/auto.29329
  96. Yik, W.Y., Steinberg, S.J., Moser, A.B., Moser, H.W., and Hacia, J.G. (2009). Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. Hum. Mutat. 30, E467-480. https://doi.org/10.1002/humu.20932
  97. Zellweger, H., Maertens, P., Superneau, D., and Wertelecki, W. (1988). History of the cerebrohepatorenal syndrome of Zellweger and other peroxisomal disorders. South Med. J. 81, 357-364. https://doi.org/10.1097/00007611-198803000-00017
  98. Zhang, Z., Suzuki, Y., Shimozawa, N., Fukuda, S., Imamura, A., Tsukamoto, T., Osumi, T., Fujiki, Y., Orii, T., Wanders, R.J., et al. (1999). Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders. Hum. Mutat. 13, 487-496. https://doi.org/10.1002/(SICI)1098-1004(1999)13:6<487::AID-HUMU9>3.0.CO;2-T
  99. Zhang, J., Tripathi, D.N., Jing, J., Alexander, A., Kim, J., Powell, R.T., Dere, R., Tait-Mulder, J., Lee, J.H., Paull, T.T., et al. (2015). ATM functions at the peroxisome to induce pexophagy in response to ROS. Nat. Cell Biol. 17, 1259-1269. https://doi.org/10.1038/ncb3230
  100. Zientara-Rytter, K., and Subramani, S. (2016). Autophagic degradation of peroxisomes in mammals. Biochem. Soc. Trans. 44, 431-440. https://doi.org/10.1042/BST20150268

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