BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Autophagy-Is it a preferred route for lifespan extension?

  • Dwivedi, Meenakshi (BK21 Life Science for Gloval Warming Team, Department of Life Science) ;
  • Ahnn, Joo-Hong (BK21 Life Science for Gloval Warming Team, Department of Life Science)
  • Published : 2009.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Autophagy, which is a process of self eating, has gained interest in the past decade due to its both beneficial and controversial roles in various biological phenomena. The discovery of autophagy genes (ATG) in yeast has led to focused research designed to elucidate the mechanism and regulation of this process. The role of autophagy in a variety of biological phenomena, including human disease, is still the subject of debate. However, recent findings suggest that autophagy is a highly regulated process with both beneficial and negative effects. Indeed, studies conducted using various model organisms have demonstrated that increased autophagy leads to an extended lifespan. Despite these findings, it is still unknown if all pathways leading to extended lifespan converge at the process of autophagy or not. Here, an overview of modern developments related to the process of autophagy, its regulation and the molecular machinery involved is presented. In addition, this review focuses on one of the beneficial aspects of autophagy, its role in lifespan regulation.

Keywords

References

  1. de Duve, C. (2005) The lysosome turns fifty. Nat. Cell Biol. 7, 847-849 https://doi.org/10.1038/ncb0905-847
  2. Tsukada, M. and Ohsumi, Y. (1993) Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett. 333, 169-174 https://doi.org/10.1016/0014-5793(93)80398-E
  3. Thumm, M., Egner, R., Koch, B., Schlumpberger, M., Straub, M., Veenhuis, M. and Wolf, D. H. (1994) Isolation of autophagocytosis mutants of Saccharomyces cerevisiae. FEBS Lett. 349, 275-280 https://doi.org/10.1016/0014-5793(94)00672-5
  4. Klionsky, D. J., Cregg, J. M., Dunn, W. A., Jr., Emr, S. D., Sakai, Y., Sandoval, I. V., Sibirny, A., Subramani, S., Thumm, M., Veenhuis, M. and Ohsumi, Y. (2003) A unified nomenclature for yeast autophagy-related genes. Dev. Cell 5, 539-545 https://doi.org/10.1016/S1534-5807(03)00296-X
  5. Shintani, T. and Klionsky, D. J. (2004) Autophagy in health and disease: a double-edged sword. Science 306, 990-995 https://doi.org/10.1126/science.1099993
  6. Chiang, H. L., Terlecky, S. R., Plant, C. P. and Dice, J. F. (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246, 382-385 https://doi.org/10.1126/science.2799391
  7. Bernales, S., Schuck, S. and Walter, P. (2007) ER-phagy: selective autophagy of the endoplasmic reticulum. Autophagy 3, 285-287 https://doi.org/10.4161/auto.3930
  8. Lemasters, J. J. (2005) Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res. 8, 3-5 https://doi.org/10.1089/rej.2005.8.3
  9. Kissova, I., Deffieu, M., Manon, S. and Camougrand, N. J. (2004) Uth1p isinvolved in the autophagic degradation of mitochondria. Biol. Chem. 279, 39068-39074 https://doi.org/10.1074/jbc.M406960200
  10. Roberts, P., Moshitch-Moshkovitz, S., Kvam, E., O'Toole, E., Winey, M. and Goldfarb, D. S. (2003) Piecemeal microautophagy of nucleus in Saccharomyces cerevisiae. Mol. Biol. Cell 14, 129-141 https://doi.org/10.1091/mbc.E02-08-0483
  11. Sakai, Y., Oku, M., van der Klei, I. J. and Kiel, J. A. (2006) Pexophagy: autophagic degradation of peroxisomes. Biochim. Biophys. Acta. 1763, 1767-1775 https://doi.org/10.1016/j.bbamcr.2006.08.023
  12. Alexander, D. E. and Leib, D. A. (2008) Xenophagy in herpes simplex virus replication and pathogenesis. Autophagy 4, 101-103 https://doi.org/10.4161/auto.5222
  13. Levine, B. (2005) Eating oneself and uninvited guests: autophagy related pathways in cellular defense. Cell 120, 159-162
  14. Kraft, C., Deplazes, A., Sohrmann, M. and Peter, M. (2008) Mature ribosomes are selectively degraded upon starvation by an autophagy pathway requiring the Ubp3p/Bre5p ubiquitin protease. Nat. Cell Biol. 10, 602-610 https://doi.org/10.1038/ncb1723
  15. Beau, I., Esclatine, A. and Codogno, P. (2008) Lost to translation: when autophagy targets mature ribosomes. Trends Cell Biol. 18, 311-314 https://doi.org/10.1016/j.tcb.2008.05.001
  16. van der Vaart, A., Mari, M. and Reggiori, F. (2008) A picky eater: exploring the mechanisms of selective autophagy in human pathologies. Traffic. 9, 281-289 https://doi.org/10.1111/j.1600-0854.2007.00674.x
  17. Levine, B. and Klionsky, D. J. (2004) Development by Self-Digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463-477 https://doi.org/10.1016/S1534-5807(04)00099-1
  18. Wang, C. W. and Klionsky, D. J. (2003) The molecular mechanism of autophagy. Mol. Med. 9, 65-76
  19. Mizushima, N. (2007) Autophagy: process and function. Genes Dev. 21, 2861-2873 https://doi.org/10.1101/gad.1599207
  20. Ohsumi, Y. (1999) Molecular mechanism of autophagy in yeast, Saccharomyces cerevisiae. Philos. Trans R. Soc. Lond B. Biol. Sci. 354, 1577-1581 https://doi.org/10.1098/rstb.1999.0501
  21. Yorimitsu, T. and Klionsky, D. J. (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ. 12, 1542-1552 https://doi.org/10.1038/sj.cdd.4401765
  22. Reggiori, F. and Klionsky, D. J. (2002) Autophagy in the eukaryotic cell. Eukaryot Cell 1, 11-21 https://doi.org/10.1128/EC.01.1.11-21.2002
  23. Stromhaug, P. E. and Klionsky, D. J. (2001) Approaching the molecular mechanism of autophagy. Traffic 2, 524-531 https://doi.org/10.1034/j.1600-0854.2001.20802.x
  24. Mortimore, G. E., Miotto, G., Venerando, R. and Kadowaki, M. (1996) Autophagy. Subcell Biochem. 27, 93-135 https://doi.org/10.1007/978-1-4615-5833-0_4
  25. Seglen, P. O., Berg, T. O., Blankson, H., Fengsrud, M.,Holen, I. and Str$\o$mhaug, P. E. (1996) Structural aspects of autophagy. Adv. Exp. Med. Biol. 389, 103-111 https://doi.org/10.1007/978-1-4613-0335-0_12
  26. Petiot, A., Pattingre, S., Arico, S., Meley, D. and Codogno, P. (2002) Diversity of signaling controls of macroautophagy in mammalian cells. Cell Struct. Funct. 27, 431-441 https://doi.org/10.1247/csf.27.431
  27. Scott, R. C., Juhász, G. and Neufeld, T. P. (2007) Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr. Biol. 17, 1-11 https://doi.org/10.1016/j.cub.2006.10.053
  28. Kametaka, S., Okano, T., Ohsumi, M. and Ohsumi, Y. (1998) Apg14p and Apg6/Vps30p form a protein complex essential for autophagy in the yeast, Saccharomyces cerevisiae. J. Biol. Chem. 273, 22284-22291 https://doi.org/10.1074/jbc.273.35.22284
  29. 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
  30. Meijer, W. H., van der Klei, I. J., Veenhuis, M. and Kiel, J. A. (2007) ATG genes involved in non-selective autophagy are conserved from yeast to man, but the selective Cvt and pexophagy pathways also require organism-specific genes. Autophagy 3, 106-116 https://doi.org/10.4161/auto.3595
  31. Tan, J. M., Wong, E. S., Kirkpatrick, D. S., Pletnikova, O., Ko, H. S., Tay, S. P., Ho, M. W., Troncoso, J., Gygi, S. P., Lee, M. K., Dawson, V. L., Dawson, T. M. and Lim, K. L. (2008) Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases. Hum. Mol. Genet. 17, 431-439 https://doi.org/10.1093/hmg/ddm320
  32. Cao, Y., Cheong, H., Song, H. and Klionsky, D. J. (2008) In vivo reconstitution of autophagy in Saccharomyces cerevisiae. J. Cell Biol. 182, 703-713 https://doi.org/10.1083/jcb.200801035
  33. Ohsumi, Y. (2001) Molecular dissection of autophagy: two ubiquitin-like systems. Nat. Rev. Mol. Cell Biol. 2, 211-216 https://doi.org/10.1038/35056522
  34. Suzuki, K. and Ohsumi, Y. (2007) Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett. 581, 2156-2161 https://doi.org/10.1016/j.febslet.2007.01.096
  35. Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T. and Ohsumi, Y. (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice ex pressing a fluorescent autophagosome marker. Mol. Biol. Cell 15, 1101-1111 https://doi.org/10.1091/mbc.E03-09-0704
  36. Melendez, A., Tallóczy, Z., Seaman, M., Eskelinen, E. L., Hall, D. H. and Levine, B. (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301, 1387-1391 https://doi.org/10.1126/science.1087782
  37. Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y. and Yoshimori, T. (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19, 5720-5728 https://doi.org/10.1093/emboj/19.21.5720
  38. Kim, J., Huang, W. P., Stromhaug, P. E. and Klionsky, D. J. (2002) Convergence of multiple autophagy and cytoplasm to vacuole targeting components to a perivacuolar membrane compartment prior to de novo vesicle formation. J. Biol. Chem. 277, 763-773 https://doi.org/10.1074/jbc.M109134200
  39. Syntichaki, P. and Tavernarakis, N. (2006) Signaling pathways regulating protein synthesis during ageing. Exp. Gerontol. 41, 1020-1025 https://doi.org/10.1016/j.exger.2006.05.014
  40. Feng, Z., Zhang, H., Levine, A. J. and Jin, S. (2005) The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. U.S.A. 102, 8204-8209 https://doi.org/10.1073/pnas.0502857102
  41. Meijer, A. J. and Codogno, P. (2007) AMP-activated protein kinase and autophagy. Autophagy 3, 238-240 https://doi.org/10.4161/auto.3710
  42. Meley, D., Bauvy, C., Houben-Weerts, J. H., Dubbelhuis, P. F., Helmond, M. T., Codogno, P. and Meijer, A. J. (2006) AMP-Activated protein kinase and the regulation of autophagic proteolysis. J. Biol. Chem. 281, 34870-34879 https://doi.org/10.1074/jbc.M605488200
  43. Hoyer-Hansen, M. and Jaattela, M. (2007) AMP-activated protein kinase: a universal regulator of autophagy? Autophagy 3, 381-383 https://doi.org/10.4161/auto.4240
  44. Klionsky, D. J. and Emr, S. D. (2000) Autophagy as a regulated pathway of cellular degradation. Science 290, 1717-1721 https://doi.org/10.1126/science.290.5497.1717
  45. Blommaart, E. F., Luiken, J. J., Blommaart, P. J., van Woerkom, G. M. and Meijer, A. J. (1995) Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J. Biol. Chem. 270, 2320-2326 https://doi.org/10.1074/jbc.270.5.2320
  46. Holen, I., Gordon, P. B. and Seglen, P. O. (1992) Protein kinase-dependent effects of okadaic acid on hepatocytic autophagy and cytoskeletal integrity. Biochem. J. 284, 633-636 https://doi.org/10.1042/bj2840633
  47. Dwivedi, M., Song, H. and Ahnn, J. (2009) Autophagy genes mediate the effect of calcineurin on life span in C. elegans. Autophagy (In press)
  48. Melendez, A. and Neufeld, T. P. (2008) The cell biology of autophagy in metazoans: a developing story. Development. 135, 2347-2360 https://doi.org/10.1242/dev.016105
  49. Kissova, I., Salin, B., Schaeffer, J., Bhatia, S., Manon, S. and Camougrand, N. (2007) Selective and non-selective autophagic degradation of mitochondria in yeast. Autophagy 3, 329-336 https://doi.org/10.4161/auto.4034
  50. Zhang, Y., Qi, H., Taylor, R., Xu, W., Liu, L. F. and Jin, S. (2007) The role of autophagy in mitochondria maintenance: characterization of mitochondrial functions in autophagy-deficient S. cerevisiae strains. Autophagy 3, 337-346 https://doi.org/10.4161/auto.4127
  51. Iwata, J., Ezaki, J., Komatsu, M., Yokota, S., Ueno, T., Tanida, I., Chiba, T., Tanaka, K. and Kominami, E. (2006) Excess peroxisomes are degraded by autophagic machinery in mammals. J. Biol. Chem. 281, 4035-4041 https://doi.org/10.1074/jbc.M512283200
  52. Ding, W. X., Ni, H. M., Gao, W., Yoshimori, T., Stolz, D. B., Ron, D. and Yin, X. M. (2007) Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am. J. Pathol. 171, 513-524 https://doi.org/10.2353/ajpath.2007.070188
  53. Levine, B. and Kroemer, G. (2008) Autophagy in the pathogenesis of disease. Cell 132, 27-42 https://doi.org/10.1016/j.cell.2007.12.018
  54. Gems, D. and Partridge, L. (2001) Insulin/IGF signalling and ageing: seeing the bigger picture. Curr. Opin. Genet. Dev. 11, 287-292 https://doi.org/10.1016/S0959-437X(00)00192-1
  55. Blagosklonny, M. V. (2008) Aging: ROS or TOR. Cell Cycle. 7, 3344-3354 https://doi.org/10.4161/cc.7.21.6965
  56. Tang, F., Watkins, J. W., Bermudez, M., Gray, R., Gaban, A., Portie, K., Grace, S., Kleve, M. and Craciun, G. (2008) A life-span extending form of autophagy employs the vacuole- vacuole fusion machinery. Autophagy 4, 874-886 https://doi.org/10.4161/auto.6556
  57. Yen, W. L. and Klionsky, D. J. (2008) How to live long and prosper: autophagy, mitochondria, and aging. Physiology (Bethesda). 23, 248-262 https://doi.org/10.1152/physiol.00013.2008
  58. Scott, R. C., Schuldiner, O. and Neufeld, T. P. (2004) Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev. Cell 7, 167-178 https://doi.org/10.1016/j.devcel.2004.07.009
  59. Simonsen, A., Cumming, R. C., Brech, A., Isakson, P., Schubert, D. R. and Finley, K. D. (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4, 176-184 https://doi.org/10.4161/auto.5269
  60. Jia, K. and Levine, B. (2007) Autophagy is required for dietary restriction- mediated life span extension in C. elegans. Autophagy 3, 597-599 https://doi.org/10.4161/auto.4989
  61. Hansen, M., Chandra, A., Mitic, L. L., Onken, B., Driscoll, M. and Kenyon, C. (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4, e24 https://doi.org/10.1371/journal.pgen.0040024
  62. Hars, E. S., Qi, H., Ryazanov, A. G., Jin, S., Cai, L., Hu, C. and Liu, L. F. (2007) Autophagy regulates ageing in C. elegans. Autophagy 3, 93-95 https://doi.org/10.4161/auto.3636
  63. Toth, M. L., Sigmond, T., Borsos, E., Barna, J., Erdelyi, P., Takacs-Vellai, K., Orosz, L., Kovacs, A. L., Csikos, G., Sass, M. and Vellai, T. (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4, 330-338 https://doi.org/10.4161/auto.5618
  64. Tavernarakis, N., Pasparaki, A., Tasdemir, E., Maiuri, M. C. and Kroemer, G. (2008) The effects of p53 on whole organism longevity are mediated by autophagy. Autophagy 4, 870-873 https://doi.org/10.4161/auto.6730
  65. Hanaoka, H., Noda, T., Shirano, Y., Kato, T., Hayashi, H.,Shibata, D., Tabata, S. and Ohsumi, Y. (2002) Leaf senescence and starvation-induced chlorosis are accelerated by the disruption of an Arabidopsis autophagy gene. Plant Physiol. 129, 1181-1193 https://doi.org/10.1104/pp.011024
  66. Doelling, J. H., Walker, J. M., Friedman, E. M., Thompson, A. R. and Vierstra, R. D. (2002) The APG8/12-activating enzyme APG7 is required for proper nutrient recycling and senescence in Arabidopsis thaliana. J. Biol. Chem. 277, 33105-33114 https://doi.org/10.1074/jbc.M204630200
  67. Donati, A., Cavallini, G., Paradiso, C., Vittorini, S., Pollera, M., Gori, Z. and Bergamini, E. (2001) Age-related changes in the autophagic proteolysis of rat isolated liver cells: ef fects of antiaging dietary restrictions. J. Gerontol. A. Biol. Sci. Med. Sci. 56, B375-383 https://doi.org/10.1093/gerona/56.9.B375
  68. Bergamini, E. (2006) Autophagy: a cell repair mechanism that retards ageing and age-associated diseases and can be intensified pharmacologically. Mol. Aspects. Med. 27, 403-410 https://doi.org/10.1016/j.mam.2006.08.001
  69. Sandoval, H., Thiagarajan, P., Dasgupta, S. K., Schumacher, A., Prchal, J. T., Chen, M. and Wang, J. (2008) Essential role for Nix in autophagic maturation of erythroid cells. Nature 454, 232-235 https://doi.org/10.1038/nature07006
  70. Pan, K. Z., Palter, J. E., Rogers, A. N., Olsen, A., Chen, D., Lithgow, G. J. and Kapahi, P. (2007) Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6, 111-119 https://doi.org/10.1111/j.1474-9726.2006.00266.x
  71. Marino, G., Ugalde, A. P., Salvador-Montoliu, N., Varela, I., Quiros, P. M., Cadinanos, J., van der Pluijm, I., Freije, J. M. and Lopez-Otin, C. (2008) Premature aging in mice activates a systemic metabolic response involving autophagy induction. Hum. Mol. Genet. 17, 2196-2211 https://doi.org/10.1093/hmg/ddn120

Cited by

  1. Does autophagy in the midgut epithelium of centipedes depend on the day/night cycle? vol.68, 2015, https://doi.org/10.1016/j.micron.2014.10.003
  2. The protective role of autophagy in experimental osteoarthritis, and the therapeutic effects of Torin 1 on osteoarthritis by activating autophagy vol.17, pp.1, 2016, https://doi.org/10.1186/s12891-016-0995-x
  3. Sucrose, But Not Glucose, Blocks IL1-β-Induced Inflammatory Response in Human Chondrocytes by Inducing Autophagy via AKT/mTOR Pathway vol.118, pp.3, 2017, https://doi.org/10.1002/jcb.25750
  4. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis vol.62, pp.3, 2010, https://doi.org/10.1002/art.27305
  5. C. elegans behavior of preference choice on bacterial food vol.28, pp.3, 2009, https://doi.org/10.1007/s10059-009-0124-x
  6. Caloric Restriction Mimetic 2-Deoxyglucose Antagonizes Doxorubicin-induced Cardiomyocyte Death by Multiple Mechanisms vol.286, pp.25, 2011, https://doi.org/10.1074/jbc.M111.225805
  7. Disruption of endocytic pathway regulatory genes activates autophagy in C. elegans vol.31, pp.5, 2011, https://doi.org/10.1007/s10059-011-1035-1
  8. The fine structure of the midgut epithelium in a centipede, Scolopendra cingulata (Chilopoda, Scolopendridae), with the special emphasis on epithelial regeneration vol.43, pp.1, 2014, https://doi.org/10.1016/j.asd.2013.06.002