Histochemistry and Cell Biology

, Volume 131, Issue 4, pp 455–458 | Cite as

Degradation of excess peroxisomes in mammalian liver cells by autophagy and other mechanisms

Review

Abstract

Here we discuss the mechanisms for the degradation of excess peroxisomes in mammalian hepatocytes which include (a) autophagy, (b) the action of peroxisomal Lon protease and (c) the membrane disrupting effect of 15-lipoxygenase. A recent study using Atg7 conditional-knock-out mice revealed that 70–80% of excess peroxisomes are degraded by the autophagic process. The remaining 20–30% of excess peroxisomes is most probably degraded by the action of peroxisomal Lon protease. Finally, a selective disruption of the peroxisomal membrane has been shown to be mediated by 15-lipoxygenase activity which is followed by diffusion of matrix proteins into the cytoplasm and cytoplasmic proteolysis.

Keywords

Peroxisome Autophagy Pexophagy Peroxisomal Lon Protease 15-Lipoxygenase Atg7-knockout mouse 

Abbreviations

DEHP

Di-(ethylhexyl)phthalate

POLP

Peroxisomal Lon Protease

References

  1. Aksam EB, Koek A, Kiel JAKW, Jourdan S, Veenhuis M, van der Klei IJ (2007) A peroxisomal Lon protease and peroxisome degradation by autophagy play key roles in vitality of Hansenula polymorpha cells. Autophagy 3:96–105PubMedGoogle Scholar
  2. Ano Y, Hattori T, Oku M, Mukaijama H, Baba M, Ohsumi Y, Kato N, Sakai Y (2005) A sorting nexin PpArg24 regulates vacuolar membrane dynamics during pexophagy via binding to phophatidylinositol-3-phosphate. Mol Biol Cell 16:446–457PubMedCrossRefGoogle Scholar
  3. Bellu AR, Komori M, van der Klei IJ, Kiel JA, Veenhuis M (2001) Peroxisome biogenesis and selective degradation converge at Pex14p. J Biol Chem 276:44570–44574PubMedCrossRefGoogle Scholar
  4. Bota DA, Davies KJA (2002) Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism. Nat Cell biol 4:674–680PubMedCrossRefGoogle Scholar
  5. Dunn WA Jr, Cregg JM, Kiel JAKW, van der Klei IJ, Oku M, Sakai Y, Sibirny AA, Stasyk OV, Veenhuis M (2005) Pexophagy. The selective autophagy of peroxisomes. Autophagy 1:75–83PubMedGoogle Scholar
  6. Fahimi HD (1973) Diffusion artefacts in cytochemistry of catalase. J Histochem Cytochem 21:999–1009PubMedGoogle Scholar
  7. Fahimi HD (1974) Effect of buffer storage on fine structure and catalase cytochemsitry of peroxisomes. J Cell Biol 63:675–683PubMedCrossRefGoogle Scholar
  8. Fahimi HD, Reinecke A, Sujata M, Yokota S, Özel M, Hartig F, Stegmeier K (1982) The short- and long-term effects of bezafibrate in the rat. Ann NY Acad Sci 386:111–133PubMedCrossRefGoogle Scholar
  9. Farre JC, Subramani S (2004) Peroxisome turnover by micropexophagy: an autophagy-related process. Trend Cell Biol 14:515–523CrossRefGoogle Scholar
  10. Hashimoto T (1982) Individual peroxisomal β-oxidation enzymes. Ann NY Acad Sci 386:5–12PubMedCrossRefGoogle Scholar
  11. Hess R, Stäubli W, Riess W (1965) Nature of the hepatomegalic effect produced by ethyl-chlorophenoxy-isobutyrate in the rat. Nature 208:856–858PubMedCrossRefGoogle Scholar
  12. Islinger M, Lüers GH, Li KW, Loos M, Völkl A (2007) Rat liver peroxisomes after fibrate treatment: a survey using quantitative mass spectrometry. J Biol Chem 282:23055–23069PubMedCrossRefGoogle Scholar
  13. Iwata J, Ezaki J, Komatsu M, Yokota S, Ueno T, Tanida I, Chiba T, Tanaka K, Kominami E (2006) Excess peroxisomes are degraded by autophagic machinery in mammals. J Biol Chem 281:4035–4041PubMedCrossRefGoogle Scholar
  14. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728PubMedCrossRefGoogle Scholar
  15. Kiel JA, Komduur JA, van der Klei IJ, Veehuis M (2003) Macropexophagy in Hansenula polymorpha: facts and views. FEBS Lett 549:1–6PubMedCrossRefGoogle Scholar
  16. Kikuchi M, Hatano N, Yokota S, Shimozawa N, Imanaka T, Taniguchi H (2004) Proteomic analysis of rat liver peroxisome. J Biol Chem 279:421–428PubMedCrossRefGoogle Scholar
  17. Kim J, Klionsky DJ (2000) Autophagy, cytoplasm-to vacuole targeting pathway, and pexophagy in yeast and mammalian cells. Annu Rev Biochem 69:303–342PubMedCrossRefGoogle Scholar
  18. Kim J, Kameda Y, Strømhaug PE, Guan J, Hefner-Gravink A, Baba M, Scott SV, Ohsumi Y, Dunn WA Jr, Klionsky DJ (2001) Cvt9/gsa9 functions in sequestering selective cytosolic cargo destined for the vacuole. J Cell Biol 153:381–396PubMedCrossRefGoogle Scholar
  19. Klionsky DJ, Ohsumi Y (1999) Vacuolar import of proteins and organelles from the cytoplasm. Annu Rev Cell Biol 15:1–32CrossRefGoogle Scholar
  20. Leighton F, Coloma L, Koenig C (1975) Structure, composition, physical properties, and turnover of proliferated peroxisomes. A study of the trophic effects of Su-13437 on rat liver. J Cell Biol 67:281–309PubMedCrossRefGoogle Scholar
  21. Monastyrska I, Klionsky DJ (2006) Autophagy in organelle homeostasis: peroxisome turnover. Mol Aspect Med 27:483–494CrossRefGoogle Scholar
  22. Osumi T, Hashimoto T (1984) The inducible fatty acid oxidation system in mammalian peroxisomes. TIBS 9:317–319Google Scholar
  23. Reddy JK, Krishnakantha TP (1975) Hepatic peroxisomes proliferation: induction by two novel compounds structurally unrelated to clofibrate. Science 190:787–789PubMedCrossRefGoogle Scholar
  24. Strømhaug PE, Bevan A, Dunn WA Jr (2001) GSA11 encodes a unique 208-kDa protein required for pexophagy and autophagy in Pichia pastoris. J Biol Chem 276:42422–42435PubMedCrossRefGoogle Scholar
  25. Suzuki CK, Suda K, Wang N, Schatz G (1994) Requirement for the yeast gene LON in intramitochondrial proteolysis and maintenance of respiration. Science 264:273–276PubMedCrossRefGoogle Scholar
  26. Tanida I, Tanida-Miyake E, Ueno T, Kominami E (2001) The human homolog of Saccharomyces cerevisiae Apg7p is a protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3. J Biol Chem 276:1701–1706PubMedGoogle Scholar
  27. Tuttle DL, Dunn WA Jr (1995) Divergent modes of autophagy in the methyltrophic yeast Pichia pastoris. J Cell Sci 108:25–35PubMedGoogle Scholar
  28. van den Bosch H, Schutgens RB, Wanders RJ, Tager JM (1992) Biochemistry of peroxisomes. Annu Rev Biochem 61:157–197PubMedCrossRefGoogle Scholar
  29. Van Dijl JM, Kutejová E, Suda K, Perecko D, Schatz G, Suzuki CK (1998) The ATPase and protease domain of yeast mitochondrial Lon: roles in proletolysis and respiration-dependent growth. Proc Natl Acad Sci USA 95:10584–10589PubMedCrossRefGoogle Scholar
  30. Van Dyck L, Pearse SA, Sherman F (1994) PIM1 encodes a mitochondrial ATP-dependent protease that is required for mitochondrial function in the yeast Saccharomyces cerevisiae. J Biol Chem 269:238–242PubMedGoogle Scholar
  31. Van Leyen K, Duvoisin RM, Engelhard H, Wiedmann M (1998) A function for lipoxygenase in programmed organelle degradation. Nature 395:392–395PubMedCrossRefGoogle Scholar
  32. Wagner I, van Dyck L, Savel’ev AS, Neupert W, Langer T (1997) Autocatalytic processing of the ATP-dependent PIM1 protease: crucial function of a pro-region for sorting to mitochondria. EMBO J 16:7317–7326PubMedCrossRefGoogle Scholar
  33. Yokota S (1986) Quantitative immunocytochemical studies on differential induction of serine pyruvate aminotransferase in mitochondria and peroxisomes of rat liver cells by administration of glucagon or di-(2-ethylhexyl)phthalate. Histochemistry 85:145–155PubMedCrossRefGoogle Scholar
  34. Yokota S (1993) Formation of autophagosomes during degradation of excess peroxisomes induced by administration of dioctyl phthalate. Eur J Cell Biol 61:67–80PubMedGoogle Scholar
  35. Yokota S, Himeno M, Roth J, Brada D, Kato K (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 62:372–383PubMedGoogle Scholar
  36. Yokota S, Himeno M, Kato K (1995) Formation of autophagosomes during degradation of excess peroxisomes induced by di-(2-ethylhexyl)phthalate treatment. III. Fusion of early autophagosomes with lysosomal compartments. Eur J Cell Biol 66:15–24PubMedGoogle Scholar
  37. Yokota S, Oda T, Fahimi HD (2001) The role of 15-lipoxygenase in disruption of the peroxisomal membrane and programmed degradation of peroxisomes in normal rat liver. J Histochem Cytochem 49:613–621PubMedGoogle Scholar
  38. Yokota S, Haraguchi CM, Oda T (2008) Induction of peroxisomal Lon protease in rat liver after di-(2-ethylhexyl)phthalate treatment. Histochem Cell Biol 129:73–83PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Section of Functional Morphology, Faculty of Pharmaceutical SciencesNagasaki International UniversitySasebo, NagasakiJapan
  2. 2.Division of Medical Cell Biology, Department of Anatomy and Cell BiologyUniversity of HeidelbergHeidelbergGermany

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