Hepatitis C virus, mitochondria and auto/mitophagy: Exploiting a host defense mechanism

World Journal of Gastroenterology

Volumn 20, Issue 10, 2014, Pages 2624-2633

  Ruggieri, Vitalba ^a   Mazzoccoli, Carmela ^a   Pazienza, Valerio ^b   Andriulli, Angelo ^b   Capitanio, Nazzareno ^c   Piccoli, Claudia ^a,c  

^a REFERRAL CANCER CENTER OF BASILICATA   (Italy)

^b CASA SOLLIEVO DELLA SOFFERENZA HOSPITAL   (Italy)

^c UNIVERSITY OF FOGGIA   (Italy)

Author keywords

Autophagy; Hepatitis C virus; Immunity; Mitochondrial dysfunctions; Mitophagy

Indexed keywords

APOLIPOPROTEIN E; GAMMA INTERFERON; LOW DENSITY LIPOPROTEIN; REACTIVE OXYGEN METABOLITE; VIRUS RNA; ANTIVIRUS AGENT;

APOPTOSIS; AUTOPHAGY; CELL DIFFERENTIATION; CELL GROWTH; CELL PROLIFERATION; ELECTRON MICROSCOPY; GENETIC VARIABILITY; GENOTYPE; HEPATITIS C; HOST RESISTANCE; IMMUNE RESPONSE; IMMUNOMODULATION; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; MITOCHONDRION; PATHOGENESIS; PHENOTYPE; PROTEIN ASSEMBLY; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; RNA REPLICATION; UNFOLDED PROTEIN RESPONSE; VIROGENESIS; VIRUS ENTRY; ANIMAL; DRUG DESIGN; DRUG EFFECTS; HEPACIVIRUS; HOST PATHOGEN INTERACTION; HUMAN; IMMUNOLOGY; MITOPHAGY; PATHOGENICITY; PATHOLOGY; VIROLOGY;

ANIMALS; ANTIVIRAL AGENTS; AUTOPHAGY; DRUG DESIGN; HEPACIVIRUS; HEPATITIS C; HOST-PATHOGEN INTERACTIONS; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DEGRADATION;

EID: 84896851743     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v20.i10.2624     Document Type: Review

References (89)

1. Kim CW, Chang KM. Hepatitis C virus: virology and life cycle. Clin Mol Hepatol 2013; 19: 17-25 [PMID: 23593605 DOI: 10.3350/cmh.2013.19.1.17]
2. Zignego AL, De Carli M, Monti M, Careccia G, La Villa G, Giannini C, D'Elios MM, Del Prete G, Gentilini P. Hepatitis C virus infection of mononuclear cells from peripheral blood and liver infiltrates in chronically infected patients. J Med Virol 1995; 47: 58-64 [PMID: 8551260]
3. Moradpour D, Penin F. Hepatitis C virus proteins: from structure to function. Curr Top Microbiol Immunol 2013; 369: 113-142 [PMID: 23463199 DOI: 10.1007/978-3-642-27340-7_5]
4. Brass V, Gouttenoire J, Wahl A, Pal Z, Blum HE, Penin F, Moradpour D. Hepatitis C virus RNA replication requires a conserved structural motif within the transmembrane domain of the NS5B RNA-dependent RNA polymerase. J Virol 2010; 84: 11580-11584 [PMID: 20739529 DOI: 10.1128/JVI.01519-10]
5. Moradpour D, Brass V, Gosert R, Wölk B, Blum HE. Hepatitis C: molecular virology and antiviral targets. Trends Mol Med 2002; 8: 476-482 [PMID: 12383770]
6. Blanchard E, Belouzard S, Goueslain L, Wakita T, Dubuisson J, Wychowski C, Rouillé Y. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J Virol 2006; 80: 6964-6972 [PMID: 16809302 DOI: 10.1128/JVI.00024-06]
7. Lindenbach BD, Rice CM. Unravelling hepatitis C virus replication from genome to function. Nature 2005; 436: 933-938 [PMID: 16107832 DOI: 10.1038/nature04077]
8. McLauchlan J. Properties of the hepatitis C virus core protein: a structural protein that modulates cellular processes. J Viral Hepat 2000; 7: 2-14 [PMID: 10718937]
9. Op De Beeck A, Cocquerel L, Dubuisson J. Biogenesis of hepatitis C virus envelope glycoproteins. J Gen Virol 2001; 82: 2589-2595 [PMID: 11602769]
10. Vieyres G, Brohm C, Friesland M, Gentzsch J, Wölk B, Roingeard P, Steinmann E, Pietschmann T. Subcellular localization and function of an epitope-tagged p7 viroporin in hepatitis C virus-producing cells. J Virol 2013; 87: 1664-1678 [PMID: 23175364 DOI: 10.1128/JVI.02782-12]
11. Murray CL, Jones CT, Rice CM. Architects of assembly: roles of Flaviviridae non-structural proteins in virion morphogenesis. Nat Rev Microbiol 2008; 6: 699-708 [PMID: 18587411 DOI: 10.1038/nrmicro1928]
12. Egger D, Wölk B, Gosert R, Bianchi L, Blum HE, Moradpour D, Bienz K. Expression of hepatitis C virus proteins induces distinct membrane alterations including a candidate viral replication complex. J Virol 2002; 76: 5974-5984 [PMID: 12021330 DOI: 10.1128/JVI.76.12.5974-5984.2002]
13. Tan SL, Katze MG. How hepatitis C virus counteracts the interferon response: the jury is still out on NS5A. Virology 2001; 284: 1-12 [PMID: 11352662 DOI: 10.1006/viro.2001.0885]
14. Blight KJ, Rice CM. Secondary structure determination of the conserved 98-base sequence at the 3' terminus of hepatitis C virus genome RNA. J Virol 1997; 71: 7345-7352 [PMID: 9311812]
15. Wölk B, Büchele B, Moradpour D, Rice CM. A dynamic view of hepatitis C virus replication complexes. J Virol 2008; 82: 10519-10531 [PMID: 18715913 DOI: 10.1128/JVI.00640-08]
16. Pawlotsky JM, Chevaliez S, McHutchison JG. The hepatitis C virus life cycle as a target for new antiviral therapies. Gastroenterology 2007; 132: 1979-1998 [PMID: 17484890]
17. Bartenschlager R, Penin F, Lohmann V, André P. Assembly of infectious hepatitis C virus particles. Trends Microbiol 2011; 19: 95-103 [PMID: 21146993 DOI: 10.1016/j.tim.2010.11.005]
18. Shulla A, Randall G. Hepatitis C virus-host interactions, replication, and viral assembly. Curr Opin Virol 2012; 2: 725-732 [PMID: 23083892 DOI: 10.1016/j.coviro.2012.09.013]
19. Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med 2001; 345: 41-52 [PMID: 11439948]
20. Hoofnagle JH. Course and outcome of hepatitis C. Hepatology 2002; 36: S21-S29 [PMID: 12407573]
21. Freeman AJ, Marinos G, Ffrench RA, Lloyd AR. Immunopathogenesis of hepatitis C virus infection. Immunol Cell Biol 2001; 79: 515-536 [PMID: 11903612]
22. Caruntu FA, Benea L. Acute hepatitis C virus infection: Diagnosis, pathogenesis, treatment. J Gastrointestin Liver Dis 2006; 15: 249-256 [PMID: 17013450]
23. Manns MP, von Hahn T. Novel therapies for hepatitis C-one pill fits all? Nat Rev Drug Discov 2013; 12: 595-610 [PMID: 23807378 DOI: 10.1038/nrd4050]
24. Liang TJ, Ghany MG. Current and future therapies for hepatitis C virus infection. N Engl J Med 2013; 368: 1907-1917 [PMID: 23675659 DOI: 10.1056/NEJMra1213651]
25. Nunnari J, Suomalainen A. Mitochondria: in sickness and in health. Cell 2012; 148: 1145-1159 [PMID: 22424226 DOI: 10.1016/j.cell.2012.02.035]
26. Barbaro G, Di Lorenzo G, Asti A, Ribersani M, Belloni G, Grisorio B, Filice G, Barbarini G. Hepatocellular mitochondrial alterations in patients with chronic hepatitis C: ultrastructural and biochemical findings. Am J Gastroenterol 1999; 94: 2198-2205 [PMID: 10445550]
27. Kageyama F, Kobayashi Y, Kawasaki T, Toyokuni S, Uchida K, Nakamura H. Successful interferon therapy reverses enhanced hepatic iron accumulation and lipid peroxidation in chronic hepatitis C. Am J Gastroenterol 2000; 95: 1041-1050 [PMID: 10763957]
28. Paradis V, Kollinger M, Fabre M, Holstege A, Poynard T, Bedossa P. In situ detection of lipid peroxidation by-products in chronic liver diseases. Hepatology 1997; 26: 135-142 [PMID: 9214462]
29. Vendemiale G, Grattagliano I, Portincasa P, Serviddio G, Palasciamo G, Altomare E. Oxidative stress in symptom-free HCV carriers: relation with ALT flare-up. Eur J Clin Invest 2001; 31: 54-63 [PMID: 11168439]
30. Serejo F, Emerit I, Filipe PM, Fernandes AC, Costa MA, Freitas JP, de Moura MC. Oxidative stress in chronic hepatitis C: the effect of interferon therapy and correlation with pathological features. Can J Gastroenterol 2003; 17: 644-650 [PMID: 14631465]
31. Moriya K, Nakagawa K, Santa T, Shintani Y, Fujie H, Miyoshi H, Tsutsumi T, Miyazawa T, Ishibashi K, Horie T, Imai K, Todoroki T, Kimura S, Koike K. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis. Cancer Res 2001; 61: 4365-4370 [PMID: 11389061]
32. Korenaga M, Wang T, Li Y, Showalter LA, Chan T, Sun J, Weinman SA. Hepatitis C virus core protein inhibits mitochondrial electron transport and increases reactive oxygen species (ROS) production. J Biol Chem 2005; 280: 37481-37488 [PMID: 16150732]
33. Wang T, Weinman SA. Causes and consequences of mitochondrial reactive oxygen species generation in hepatitis C. J Gastroenterol Hepatol 2006; 21 Suppl 3: S34-S37 [PMID: 16958669]
34. Wang T, Campbell RV, Yi MK, Lemon SM, Weinman SA. Role of Hepatitis C virus core protein in viral-induced mitochondrial dysfunction. J Viral Hepat 2010; 17: 784-793 [PMID: 20002299 DOI: 10.1111/j.1365-2893.2009.01238.x]
35. Schwer B, Ren S, Pietschmann T, Kartenbeck J, Kaehlcke K, Bartenschlager R, Yen TS, Ott M. Targeting of hepatitis C virus core protein to mitochondria through a novel C-terminal localization motif. J Virol 2004; 78: 7958-7968 [PMID: 15254168]
36. Wang T, Weinman SA. Interactions Between Hepatitis C Virus and Mitochondria: Impact on Pathogenesis and Innate Immunity. Curr Pathobiol Rep 2013; 1: 179-187 [PMID: 23956955]
37. Machida K, Cheng KT, Lai CK, Jeng KS, Sung VM, Lai MM. Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation. J Virol 2006; 80: 7199-7207 [PMID: 16809325]
38. Nomura-Takigawa Y, Nagano-Fujii M, Deng L, Kitazawa S, Ishido S, Sada K, Hotta H. Non-structural protein 4A of Hepatitis C virus accumulates on mitochondria and renders the cells prone to undergoing mitochondria-mediated apoptosis. J Gen Virol 2006; 87: 1935-1945 [PMID: 16760395]
39. Gong G, Waris G, Tanveer R, Siddiqui A. Human hepatitis C virus NS5A protein alters intracellular calcium levels, induces oxidative stress, and activates STAT-3 and NF-kappa B. Proc Natl Acad Sci USA 2001; 98: 9599-9604 [PMID: 11481452]
40. Robinson LC, Marchant JS. Enhanced Ca2+ leak from ER Ca2+ stores induced by hepatitis C NS5A protein. Biochem Biophys Res Commun 2008; 368: 593-599 [PMID: 18258181 DOI: 10.1016/j.bbrc.2008.01.127]
41. Dionisio N, Garcia-Mediavilla MV, Sanchez-Campos S, Majano PL, Benedicto I, Rosado JA, Salido GM, Gonzalez-Gallego J. Hepatitis C virus NS5A and core proteins induce oxidative stress-mediated calcium signalling alterations in hepatocytes. J Hepatol 2009; 50: 872-882 [PMID: 19303156 DOI: 10.1016/j.jhep.2008.12.026]
42. Rizzuto R, Simpson AW, Brini M, Pozzan T. Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin. Nature 1992; 358: 325-327 [PMID: 1322496]
43. Williams GS, Boyman L, Chikando AC, Khairallah RJ, Lederer WJ. Mitochondrial calcium uptake. Proc Natl Acad Sci USA 2013; 110: 10479-10486 [PMID: 23759742 DOI: 10.1073/ pnas.1300410110]
44. Rizzuto R, Pozzan T. Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev 2006; 86: 369-408 [PMID: 16371601]
45. Rimessi A, Giorgi C, Pinton P, Rizzuto R. The versatility of mitochondrial calcium signals: from stimulation of cell metabolism to induction of cell death. Biochim Biophys Acta 2008; 1777: 808-816 [PMID: 18573473 DOI: 10.1016/j.bbabio.2008.05.449]
46. Hansford RG, Zorov D. Role of mitochondrial calcium transport in the control of substrate oxidation. Mol Cell Biochem 1998; 184: 359-369 [PMID: 9746330]
47. McCormack JG, Denton RM. Mitochondrial Ca2+ transport and the role of intramitochondrial Ca2+ in the regulation of energy metabolism. Dev Neurosci 1993; 15: 165-173 [PMID: 7805568]
48. Ichas F, Mazat JP. From calcium signaling to cell death: two conformations for the mitochondrial permeability transition pore. Switching from low-to high-conductance state. Biochim Biophys Acta 1998; 1366: 33-50 [PMID: 9714722]
49. Piccoli C, Scrima R, Quarato G, D'Aprile A, Ripoli M, Lecce L, Boffoli D, Moradpour D, Capitanio N. Hepatitis C virus protein expression causes calcium-mediated mitochondrial bioenergetic dysfunction and nitro-oxidative stress. Hepatology 2007; 46: 58-65 [PMID: 17567832]
50. Quarato G, Scrima R, Agriesti F, Moradpour D, Capitanio N, Piccoli C. Targeting mitochondria in the infection strategy of the hepatitis C virus. Int J Biochem Cell Biol 2013; 45: 156-166 [PMID: 22710347 DOI: 10.1016/j.biocel.2012.06.008]
51. Benali-Furet NL, Chami M, Houel L, De Giorgi F, Vernejoul F, Lagorce D, Buscail L, Bartenschlager R, Ichas F, Rizzuto R, Paterlini-Bréchot P. Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion. Oncogene 2005; 24: 4921-4933 [PMID: 15897896]
52. Tardif KD, Mori K, Siddiqui A. Hepatitis C virus subgenomic replicons induce endoplasmic reticulum stress activating an intracellular signaling pathway. J Virol 2002; 76: 7453-7459 [PMID: 12097557]
53. Waris G, Tardif KD, Siddiqui A. Endoplasmic reticulum (ER) stress: hepatitis C virus induces an ER-nucleus signal transduction pathway and activates NF-kappaB and STAT-3. Biochem Pharmacol 2002; 64: 1425-1430 [PMID: 12417255]
54. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009; 417: 1-13 [PMID: 19061483 DOI: 10.1042/BJ20081386]
55. Di Lisa F, Menabò R, Canton M, Barile M, Bernardi P. Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in postischemic reperfusion of the heart. J Biol Chem 2001; 276: 2571-2575 [PMID: 11073947]
56. Brookes PS, Yoon Y, Robotham JL, Anders MW, Sheu SS. Calcium, ATP, and ROS: a mitochondrial love-hate triangle. Am J Physiol Cell Physiol 2004; 287: C817-C833 [PMID: 15355853]
57. Ripoli M, D'Aprile A, Quarato G, Sarasin-Filipowicz M, Gouttenoire J, Scrima R, Cela O, Boffoli D, Heim MH, Moradpour D, Capitanio N, Piccoli C. Hepatitis C virus-linked mitochondrial dysfunction promotes hypoxia-inducible factor 1 alpha-mediated glycolytic adaptation. J Virol 2010; 84: 647-660 [PMID: 19846525 DOI: 10.1128/JVI.00769-09]
58. Nasimuzzaman M, Waris G, Mikolon D, Stupack DG, Siddiqui A. Hepatitis C virus stabilizes hypoxia-inducible factor 1alpha and stimulates the synthesis of vascular endothelial growth factor. J Virol 2007; 81: 10249-10257 [PMID: 17626077]
59. Rasola A, Bernardi P. The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis. Apoptosis 2007; 12: 815-833 [PMID: 17294078]
60. Seth RB, Sun L, Ea CK, Chen ZJ. Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 2005; 122: 669-682 [PMID: 16125763]
61. Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB. VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 2005; 19: 727-740 [PMID: 16153868]
62. Arnoult D, Soares F, Tattoli I, Girardin SE. Mitochondria in innate immunity. EMBO Rep 2011; 12: 901-910 [PMID: 21799518 DOI: 10.1038/embor.2011.157]
63. Li XD, Sun L, Seth RB, Pineda G, Chen ZJ. Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc Natl Acad Sci USA 2005; 102: 17717-17722 [PMID: 16301520]
64. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005; 39: 359-407 [PMID: 16285865]
65. Gelino S, Hansen M. Autophagy-An Emerging Anti-Aging Mechanism. J Clin Exp Pathol 2012; Suppl 4: pii: 006 [PMID: 23750326]
66. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008; 132: 27-42 [PMID: 18191218 DOI: 10.1016/ j.cell.2007.12.018]
67. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007; 8: 741-752 [PMID: 17717517]
68. Mizushima N. Autophagy: process and function. Genes Dev 2007; 21: 2861-2873 [PMID: 18006683 DOI: 10.1101/ gad.1599207]
69. Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, Levine B. Induction of autophagy and inhibition of tumorigenesis by beclin 1. Nature 1999; 402: 672-676 [PMID: 10604474]
70. Ashrafi G, Schwarz TL. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ 2013; 20: 31-42 [PMID: 22743996 DOI: 10.1038/cdd.2012.81]
71. Goldman SJ, Taylor R, Zhang Y, Jin S. Autophagy and the degradation of mitochondria. Mitochondrion 2010; 10: 309-315 [PMID: 20083234 DOI: 10.1016/j.mito.2010.01.005]
72. Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol 2011; 12: 9-14 [PMID: 21179058 DOI: 10.1038/ nrm3028]
73. Okamoto K, Kondo-Okamoto N. Mitochondria and autophagy: critical interplay between the two homeostats. Biochim Biophys Acta 2012; 1820: 595-600 [PMID: 21846491 DOI: 10.1016/j.bbagen.2011.08.001]
74. Narendra D, Tanaka A, Suen DF, Youle RJ. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 2008; 183: 795-803 [PMID: 19029340 DOI: 10.1083/jcb.200809125]
75. Yoshii SR, Kishi C, Ishihara N, Mizushima N. Parkin mediates proteasome-dependent protein degradation and rupture of the outer mitochondrial membrane. J Biol Chem 2011; 286: 19630-19640 [PMID: 21454557 DOI: 10.1074/jbc. M110.209338]
76. Ding WX, Yin XM. Mitophagy: mechanisms, pathophysiological roles, and analysis. Biol Chem 2012; 393: 547-564 [PMID: 22944659 DOI: 10.1515/hsz-2012-0119]
77. 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: 1037-1040 [PMID: 15528445]
78. Paludan C, Schmid D, Landthaler M, Vockerodt M, Kube D, Tuschl T, Münz C. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 2005; 307: 593-596 [PMID: 15591165]
79. Deretic V. Autophagy as an innate immunity paradigm: expanding the scope and repertoire of pattern recognition receptors. Curr Opin Immunol 2012; 24: 21-31 [PMID: 22118953 DOI: 10.1016/j.coi.2011.10.006]
80. Riley-Vargas RC, Gill DB, Kemper C, Liszewski MK, Atkinson JP. CD46: expanding beyond complement regulation. Trends Immunol 2004; 25: 496-503 [PMID: 15324743]
81. Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, Herman B, Levine B. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J Virol 1998; 72: 8586-8596 [PMID: 9765397]
82. Dreux M, Chisari FV. Viruses and the autophagy machinery. Cell Cycle 2010; 9: 1295-1307 [PMID: 20305376]
83. Levine B, Mizushima N, Virgin HW. Autophagy in immunity and inflammation. Nature 2011; 469: 323-335 [PMID: 21248839 DOI: 10.1038/nature09782]
84. Dreux M, Gastaminza P, Wieland SF, Chisari FV. The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci USA 2009; 106: 14046-14051 [PMID: 19666601 DOI: 10.1073/pnas.0907344106]
85. Ke PY, Chen SS. Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J Clin Invest 2011; 121: 37-56 [PMID: 21135505 DOI: 10.1172/JCI41474]
86. Sir D, Chen WL, Choi J, Wakita T, Yen TS, Ou JH. Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology 2008; 48: 1054-1061 [PMID: 18688877 DOI: 10.1002/hep.22464]
87. Zheng Y, Gao B, Ye L, Kong L, Jing W, Yang X, Wu Z, Ye L. Hepatitis C virus non-structural protein NS4B can modulate an unfolded protein response. J Microbiol 2005; 43: 529-536 [PMID: 16410770]
88. Chu VC, Bhattacharya S, Nomoto A, Lin J, Zaidi SK, Oberley TD, Weinman SA, Azhar S, Huang TT. Persistent expression of hepatitis C virus non-structural proteins leads to increased autophagy and mitochondrial injury in human hepatoma cells. PLoS One 2011; 6: e28551 [PMID: 22164304 DOI: 10.1371/journal.pone.0028551]
89. Kim SJ, Syed GH, Siddiqui A. Hepatitis C virus induces the mitochondrial translocation of Parkin and subsequent mitophagy. PLoS Pathog 2013; 9: e1003285 [PMID: 23555273 DOI: 10.1371/journal.ppat.1003285]