Experimental and Molecular Medicine

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

DOI QR Code

Why is autophagy important in human diseases?

  • Jing, Kaipeng (Department of Biochemistry, College of Medicine, Chungnam National University) ;
  • Lim, Kyu (Department of Biochemistry, College of Medicine, Chungnam National University)
  • Accepted : 2011.12.08
  • Published : 2012.02.29
⟨ Previous Next ⟩

Abstract

The process of macroautophagy (referred to hereafter as autophagy), is generally characterized by the prominent formation of autophagic vesicles in the cytoplasm. In the past decades, studies of autophagy have been vastly expanded. As an essential process to maintain cellular homeostasis and functions, autophagy is responsible for the lysosome-mediated degradation of damaged proteins and organelles, and thus misregulation of autophagy can result in a variety of pathological conditions in human beings. Although our understanding of regulatory pathways that control autophagy is still limited, an increasing number of studies have shed light on the importance of autophagy in a wide range of physiological processes and human diseases. The goal of the reviews in the current issue is to provide a general overview of current knowledge on autophagy. The machinery and regulation of autophagy were outlined with special attention to its role in diabetes, neurodegenerative disorders, infectious diseases and cancer.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

References

  1. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB. Autophagy inhibition enhances therapy-induced apoptosis in a Mycinduced model of lymphoma. J Clin Invest 2007;117:326-36 https://doi.org/10.1172/JCI28833
  2. Berry DL, Baehrecke EH. Growth arrest and autophagy are required for salivary gland cell degradation in Drosophila. Cell 2007;131:1137-48 https://doi.org/10.1016/j.cell.2007.10.048
  3. Deter RL, Baudhuin P, De Duve C. Participation of lysosomes in cellular autophagy induced in rat liver by glucagon. J Cell Biol 1967;35:C11-6 https://doi.org/10.1083/jcb.35.2.C11
  4. Ebato C, Uchida T, Arakawa M, Komatsu M, Ueno T, Komiya K, Azuma K, Hirose T, Tanaka K, Kominami E, Kawamori R, Fujitani Y, Watada H. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet. Cell Metab 2008;8:325-32 https://doi.org/10.1016/j.cmet.2008.08.009
  5. Goldman SJ, Zhang Y, Jin S. Autophagic degradation of mitochondria in white adipose tissue differentiation. Antioxid Redox Signal 2011;14:1971-8 https://doi.org/10.1089/ars.2010.3777
  6. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 2004;119:753-66 https://doi.org/10.1016/j.cell.2004.11.038
  7. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006;441:885-9 https://doi.org/10.1038/nature04724
  8. Jing K, Song KS, Shin S, Kim N, Jeong S, Oh HR, Park JH, Seo KS, Heo JY, Han J, Park JI, Han C, Wu T, Kweon GR, Park SK, Yoon WH, Hwang BD, Lim K. Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling and promotes apoptosis in human cancer cells harboring wild-type p53. Autophagy 2011;7:1348-58 https://doi.org/10.4161/auto.7.11.16658
  9. Johansen T, Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 2011;7:279-96 https://doi.org/10.4161/auto.7.3.14487
  10. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science 2000;290:1717-21 https://doi.org/10.1126/science.290.5497.1717
  11. Levine B, Deretic V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 2007;7:767-77 https://doi.org/10.1038/nri2161
  12. Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, Simon AK. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci USA 2010;107:832-7 https://doi.org/10.1073/pnas.0913170107
  13. Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, Kamimoto T, Nara A, Funao J, Nakata M, Tsuda K, Hamada S, Yoshimori T. Autophagy defends cells against invading group A Streptococcus. Science 2004; 306:1037-40 https://doi.org/10.1126/science.1103966
  14. Nedelsky NB, Todd PK, Taylor JP. Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection. Biochim Biophys Acta 2008;1782:691-9 https://doi.org/10.1016/j.bbadis.2008.10.002
  15. Qu X, Zou Z, Sun Q, Luby-Phelps K, Cheng P, Hogan RN, Gilpin C, Levine B. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 2007;128:931-46 https://doi.org/10.1016/j.cell.2006.12.044
  16. Rubinsztein DC. The roles of intracellular protein-degradation pathways in neurodegeneration. Nature 2006;443:780-6 https://doi.org/10.1038/nature05291
  17. Shao Y, Gao Z, Marks PA, Jiang X. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc Natl Acad Sci USA 2004;101:18030-5 https://doi.org/10.1073/pnas.0408345102
  18. Shin DM, Yuk JM, Lee HM, Lee SH, Son JW, Harding CV, Kim JM, Modlin RL, Jo EK. Mycobacterial lipoprotein activates autophagy via TLR2/1/CD14 and a functional vitamin D receptor signalling. Cell Microbiol 2010;12:1648-65 https://doi.org/10.1111/j.1462-5822.2010.01497.x
  19. Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 2006;313:1438-41 https://doi.org/10.1126/science.1129577
  20. Song KS, Kim JS, Yun EJ, Kim YR, Seo KS, Park JH, Jung YJ, Park JI, Kweon GR, Yoon WH, Lim K, Hwang BD. Rottlerin induces autophagy and apoptotic cell death through a PKC-delta-independent pathway in HT1080 human fibrosarcoma cells: the protective role of autophagy in apoptosis. Autophagy 2008;4:650-8 https://doi.org/10.4161/auto.6057
  21. Talloczy Z, Virgin HW 4th, Levine B. PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2006;2:24-9 https://doi.org/10.4161/auto.2176
  22. Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae. FEBS Lett 1993;333:169-74 https://doi.org/10.1016/0014-5793(93)80398-E
  23. Xie Z, Nair U, Klionsky DJ. Atg8 controls phagophore expansion during autophagosome formation. Mol Biol Cell 2008;19:3290-8 https://doi.org/10.1091/mbc.E07-12-1292
  24. Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 2006;8:1124-32 https://doi.org/10.1038/ncb1482
  25. Yu L, Wan F, Dutta S, Welsh S, Liu Z, Freundt E, Baehrecke EH, Lenardo M. Autophagic programmed cell death by selective catalase degradation. Proc Natl Acad Sci USA 2006;103:4952-7 https://doi.org/10.1073/pnas.0511288103
  26. Yuk JM, Shin DM, Song KS, Lim K, Kim KH, Lee SH, Kim JM, Lee JS, Paik TH, Kim JS, Jo EK. Bacillus calmette-guerin cell wall cytoskeleton enhances colon cancer radiosensitivity through autophagy. Autophagy 2010;6:46-60 https://doi.org/10.4161/auto.6.1.10325

Cited by

  1. Transcriptional Regulation by Nuclear Corepressors and PGC-1 α : Implications for Mitochondrial Quality Control and Insulin Sensitivity vol.2012, pp.None, 2012, https://doi.org/10.1155/2012/348245
  2. Inhibition of Autophagy by Sera From Pregnant Women vol.20, pp.11, 2012, https://doi.org/10.1177/1933719113485301
  3. The Omega-3 Polyunsaturated Fatty Acid DHA Induces Simultaneous Apoptosis and Autophagy via Mitochondrial ROS-Mediated Akt-mTOR Signaling in Prostate Cancer Cells Expressing Mutant p53 vol.2013, pp.None, 2012, https://doi.org/10.1155/2013/568671
  4. 인체 구강암 세포주에서 Docosahexaenoic acid에 의한 세포독성 기전 vol.23, pp.5, 2012, https://doi.org/10.5352/jls.2013.23.5.689
  5. High glucose-induced oxidative stress promotes autophagy through mitochondrial damage in rat notochordal cells vol.37, pp.12, 2012, https://doi.org/10.1007/s00264-013-2037-8
  6. Elastase induces lung epithelial cell autophagy through placental growth factor: a new insight of emphysema pathogenesis. vol.10, pp.9, 2012, https://doi.org/10.4161/auto.29190
  7. High Glucose Accelerates Autophagy in Adult Rat Intervertebral Disc Cells vol.8, pp.5, 2012, https://doi.org/10.4184/asj.2014.8.5.543
  8. Role of autophagy and its significance in cellular homeostasis vol.98, pp.12, 2012, https://doi.org/10.1007/s00253-014-5721-8
  9. Overnutrition, mTOR signaling, and cardiovascular diseases vol.307, pp.10, 2012, https://doi.org/10.1152/ajpregu.00262.2014
  10. A new genetic model for calcium induced autophagy and ER-stress in Drosophila photoreceptor cells vol.9, pp.1, 2012, https://doi.org/10.4161/19336950.2014.981439
  11. Baicalein Triggers Autophagy and Inhibits the Protein Kinase B/Mammalian Target of Rapamycin Pathway in Hepatocellular Carcinoma HepG2 Cells vol.29, pp.5, 2012, https://doi.org/10.1002/ptr.5298
  12. Applications of phototransformable fluorescent proteins for tracking the dynamics of cellular components vol.14, pp.10, 2012, https://doi.org/10.1039/c5pp00174a
  13. Autophagy Gene Activity May Act As a Key Factor for Sensitivity of Tumor Cells to Oncolytic Vesicular Stomatitis Virus vol.9, pp.1, 2012, https://doi.org/10.17795/ijcp-3919
  14. Autophagy regulates death of retinal pigment epithelium cells in age-related macular degeneration vol.33, pp.2, 2012, https://doi.org/10.1007/s10565-016-9371-8
  15. Hydrogel Environment Supports Cell Culture Expansion of a Grade IV Astrocytoma vol.42, pp.9, 2012, https://doi.org/10.1007/s11064-017-2308-7
  16. Adoptive Autophagy Activation: a Much-Needed Remedy Against Chemical Induced Neurotoxicity/Developmental Neurotoxicity vol.54, pp.3, 2012, https://doi.org/10.1007/s12035-016-9778-5
  17. Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide vol.39, pp.6, 2012, https://doi.org/10.1177/1010428317702901
  18. Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet vol.21, pp.3, 2017, https://doi.org/10.20463/jenb.2017.0013
  19. Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion vol.23, pp.48, 2012, https://doi.org/10.3748/wjg.v23.i48.8443
  20. TAK1 mediates excessive autophagy via p38 and ERK in cisplatin‐induced acute kidney injury vol.22, pp.5, 2012, https://doi.org/10.1111/jcmm.13585
  21. Effect on the liver cancer cell invasion ability by studying the associations between autophagy and TRAP1 expression vol.16, pp.1, 2012, https://doi.org/10.3892/ol.2018.8774
  22. Inhibition of autophagy initiation potentiates chemosensitivity in mesothelioma vol.57, pp.3, 2012, https://doi.org/10.1002/mc.22757
  23. Effects of 8 Weeks Calorie Reduction and Resistance Exercise on Traf2-NFkB-mTOR and SIRT1-FoxO1 Signal Expression of Cardiac Muscle in High-fat Induced Obese Middle-Aged Rats vol.27, pp.2, 2012, https://doi.org/10.15857/ksep.2018.27.2.126
  24. α-Viniferin activates autophagic apoptosis and cell death by reducing glucocorticoid receptor expression in castration-resistant prostate cancer cells vol.35, pp.7, 2012, https://doi.org/10.1007/s12032-018-1163-y
  25. Interleukin-12p35 Knock Out Aggravates Doxorubicin-Induced Cardiac Injury and Dysfunction by Aggravating the Inflammatory Response, Oxidative Stress, Apoptosis and Autophagy in Mice vol.35, pp.None, 2018, https://doi.org/10.1016/j.ebiom.2018.06.009
  26. Apatinib-induced protective autophagy and apoptosis through the AKT–mTOR pathway in anaplastic thyroid cancer vol.9, pp.10, 2012, https://doi.org/10.1038/s41419-018-1054-3
  27. The Role of Autophagy in Eosinophilic Airway Inflammation vol.19, pp.1, 2012, https://doi.org/10.4110/in.2019.19.e5
  28. Expression and epigenetic regulatory mechanism of BNIP3 in clear cell renal cell carcinoma vol.54, pp.1, 2019, https://doi.org/10.3892/ijo.2018.4603
  29. Bioenergetics and Autophagic Imbalance in Patients-Derived Cell Models of Parkinson Disease Supports Systemic Dysfunction in Neurodegeneration vol.13, pp.None, 2019, https://doi.org/10.3389/fnins.2019.00894
  30. Baseline Serum Levels of Beclin-1, but Not Inflammatory Factors, May Predict Antidepressant Treatment Response in Chinese Han Patients With MDD: A Preliminary Study vol.10, pp.None, 2012, https://doi.org/10.3389/fpsyt.2019.00378
  31. Overexpression of miR‐138‐5p suppresses MnCl2‐induced autophagy by targeting SIRT1 in SH‐SY5Y cells vol.34, pp.4, 2019, https://doi.org/10.1002/tox.22708
  32. Interplay between ER stress and autophagy: A possible mechanism in multiple sclerosis pathology vol.108, pp.None, 2019, https://doi.org/10.1016/j.yexmp.2019.04.016
  33. LIR Motif-Containing Hyperdisulfide β-Ginkgotide is Cytoprotective, Adaptogenic, and Scaffold-Ready vol.24, pp.13, 2012, https://doi.org/10.3390/molecules24132417
  34. Deoxynivalenol-Induced Cytotoxicity and Apoptosis in IPEC-J2 Cells Through the Activation of Autophagy by Inhibiting PI3K-AKT-mTOR Signaling Pathway vol.4, pp.19, 2019, https://doi.org/10.1021/acsomega.9b03208
  35. Role of skeletal muscle autophagy in high-fat-diet-induced obesity and exercise vol.78, pp.1, 2012, https://doi.org/10.1093/nutrit/nuz044
  36. Protective Effect of Metformin against Hydrogen Peroxide-Induced Oxidative Damage in Human Retinal Pigment Epithelial (RPE) Cells by Enhancing Autophagy through Activation of AMPK Pathway vol.2020, pp.None, 2012, https://doi.org/10.1155/2020/2524174
  37. NlATG1 Gene Participates in Regulating Autophagy and Fission of Mitochondria in the Brown Planthopper, Nilaparvata lugens vol.10, pp.None, 2012, https://doi.org/10.3389/fphys.2019.01622
  38. miR-29c-3p inhibits autophagy and cisplatin resistance in ovarian cancer by regulating FOXP1/ATG14 pathway vol.19, pp.2, 2012, https://doi.org/10.1080/15384101.2019.1704537
  39. Advances in Understanding the Effects of Erythropoietin on Renal Fibrosis vol.7, pp.None, 2020, https://doi.org/10.3389/fmed.2020.00047
  40. Apoptosis and autophagy as a turning point in viral-host interactions: the case of human norovirus and its surrogates vol.15, pp.3, 2020, https://doi.org/10.2217/fvl-2019-0111
  41. Anti‐interleukin‐5‐neutralizing antibody attenuates caradiac injury and cadiac dysfunction by aggravating the inflammatory response in doxorubicin‐treated mice vol.44, pp.6, 2020, https://doi.org/10.1002/cbin.11330
  42. Circ-ADAM9 targeting PTEN and ATG7 promotes autophagy and apoptosis of diabetic endothelial progenitor cells by sponging mir-20a-5p vol.11, pp.7, 2012, https://doi.org/10.1038/s41419-020-02745-x
  43. Trehalose Inhibits Human Immunodeficiency Virus Type 1 Infection in Primary Human Macrophages and CD4+ T Lymphocytes through Two Distinct Mechanisms vol.94, pp.17, 2020, https://doi.org/10.1128/jvi.00237-20
  44. Allicin reduces inflammation by regulating ROS/NLRP3 and autophagy in the context of A. fumigatus infection in mice vol.762, pp.None, 2012, https://doi.org/10.1016/j.gene.2020.145042
  45. PLEKHG5 regulates autophagy, survival and MGMT expression in U251-MG glioblastoma cells vol.10, pp.1, 2020, https://doi.org/10.1038/s41598-020-77958-3
  46. Effects of Dietary Inclusion of Clostridium autoethanogenum Protein on the Growth Performance and Liver Health of Largemouth Bass (Micropterus salmoides) vol.8, pp.None, 2021, https://doi.org/10.3389/fmars.2021.764964
  47. Autophagy in Viral Development and Progression of Cancer vol.11, pp.None, 2021, https://doi.org/10.3389/fonc.2021.603224
  48. Cellular Signal Transductions and Their Inhibitors Derived from Deep-Sea Organisms vol.19, pp.4, 2012, https://doi.org/10.3390/md19040205
  49. MiR-15a-5p Confers Chemoresistance in Acute Myeloid Leukemia by Inhibiting Autophagy Induced by Daunorubicin vol.22, pp.10, 2012, https://doi.org/10.3390/ijms22105153
  50. Qingfei oral liquid inhibited autophagy to alleviate inflammation via mTOR signaling pathway in RSV-infected asthmatic mice vol.138, pp.None, 2012, https://doi.org/10.1016/j.biopha.2021.111449
  51. Autophagic Pathways to Clear the Tau Aggregates in Alzheimer’s Disease vol.41, pp.6, 2012, https://doi.org/10.1007/s10571-020-00897-0
  52. Synthesis of Indofulvin Pseudo‐Natural Products Yields a New Autophagy Inhibitor Chemotype vol.8, pp.19, 2012, https://doi.org/10.1002/advs.202102042
  53. New Insights into Intestinal Permeability in Irritable Bowel Syndrome-Like Disorders: Histological and Ultrastructural Findings of Duodenal Biopsies vol.10, pp.10, 2012, https://doi.org/10.3390/cells10102593
  54. SWCNH (Single walled carbon nanohorn) supervises ER (Endoplasmic reticulum) stress through triggering autophagy process of hepatocytes, especially in hepatoma cell line HepG2 vol.8, pp.12, 2021, https://doi.org/10.1088/2053-1591/ac452b
  55. LCN2 deficiency ameliorates doxorubicin-induced cardiomyopathy in mice vol.588, pp.None, 2022, https://doi.org/10.1016/j.bbrc.2021.12.048
  56. Toll-like receptor 4 mutation protects the kidney from Ang-II-induced hypertensive injury vol.175, pp.None, 2012, https://doi.org/10.1016/j.phrs.2021.106030
  57. Phenethyl isothiocyanate as an anti-nutritional factor attenuates deoxynivalenol-induced IPEC-J2 cell injury through inhibiting ROS-mediated autophagy vol.8, pp.1, 2012, https://doi.org/10.1016/j.aninu.2021.09.013