Operation of mitochondrial machinery in viral infection-induced immune responses

Jenn-Haung Lai, Shue-Fen Luo, Ling-Jun Ho, Jenn-Haung Lai, Shue-Fen Luo, Ling-Jun Ho

Abstract

Mitochondria have been recognized as ancient bacteria that contain evolutionary endosymbionts. Metabolic pathways and inflammatory signals interact within mitochondria in response to different stresses, such as viral infections. In this commentary, we address several interesting questions, including (1) how do mitochondrial machineries participate in immune responses; (2) how do mitochondria mediate antiviral immunity; (3) what mechanisms involved in mitochondrial machinery, including the downregulation of mitochondrial DNA (mtDNA), disturbances of mitochondrial dynamics, and the induction of mitophagy and regulation of apoptosis, have been adopted by viruses to evade antiviral immunity; (4) what mechanisms involve the regulation of mitochondrial machineries in antiviral therapeutics; and (5) what are the potential challenges and perspectives in developing mitochondria-targeting antiviral treatments? This commentary provides a comprehensive review of the roles and mechanisms of mitochondrial machineries in immunity, viral infections and related antiviral therapeutics.

Keywords: Immune; Mitochondria; Therapy; Virus.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Regulation of mitochondrial machineries by viruses to antagonize immune defense. Viral infection triggers antiviral immunity in host cells leading to the production of antiviral IFNs. Mitochondria play crucial roles in antiviral immunity. In order to evade antiviral immunity, viruses target interfering mitochondrial function or causing mitochondrial elimination (mitophagy). Several major strategies are developed by viruses to achieve the goals. These include at least the disturbance of mitochondrial dynamics, the induction of mitophagy, the suppression of mtDNA copy number or interfering mtDNA-mediated effects as well as the regulation of apoptotic processes. stands for inducing and stands for suppressing.

References

    1. Brubaker S.W., Bonham K.S., Zanoni I., Kagan J.C. Innate immune pattern recognition: a cell biological perspective. Annu. Rev. Immunol. 2015;33:257–290.
    1. Bardoel B.W., Strijp J.A. Molecular battle between host and bacterium: recognition in innate immunity. J. Mol. Recognit. 2011;24:1077–1086.
    1. Bayne C.J. Origins and evolutionary relationships between the innate and adaptive arms of immune systems. Integr. Comp. Biol. 2003;43:293–299.
    1. Liston A., Masters S.L. Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat. Rev. Immunol. 2017;17:208–214.
    1. Kato H., Sato S., Yoneyama M., Yamamoto M., Uematsu S., Matsui K. Cell type-specific involvement of RIG-I in antiviral response. Immunity. 2005;23:19–28.
    1. Kowalinski E., Lunardi T., McCarthy A.A., Louber J., Brunel J., Grigorov B. Structural basis for the activation of innate immune pattern-recognition receptor RIG-I by viral RNA. Cell. 2011;147:423–435.
    1. Hou F., Sun L., Zheng H., Skaug B., Jiang Q.X., Chen Z.J. MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell. 2011;146:448–461.
    1. Qi N., Shi Y., Zhang R., Zhu W., Yuan B., Li X. Multiple truncated isoforms of MAVS prevent its spontaneous aggregation in antiviral innate immune signalling. Nat. Commun. 2017;8:15676.
    1. Heaton S.M., Borg N.A., Dixit V.M. Ubiquitin in the activation and attenuation of innate antiviral immunity. J. Exp. Med. 2016;213:1–13.
    1. Liu S., Cai X., Wu J., Cong Q., Chen X., Li T. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015;347 aaa2630.
    1. Dromparis P., Michelakis E.D. Mitochondria in vascular health and disease. Annu. Rev. Physiol. 2013;75:95–126.
    1. van der Burgh R., Boes M. Mitochondria in autoinflammation: cause, mediator or bystander? Trends Endocrinol. Metab. 2015;26:263–271.
    1. Prochnicki T., Latz E. Inflammasomes on the crossroads of innate immune recognition and metabolic control. Cell Metab. 2017;26:71–93.
    1. Monlun M., Hyernard C., Blanco P., Lartigue L., Faustin B. Mitochondria as molecular platforms integrating multiple innate immune signalings. J. Mol. Biol. 2017;429:1–13.
    1. Kurose I., Miura S., Fukumura D., Yonei Y., Saito H., Tada S. Nitric oxide mediates Kupffer cell-induced reduction of mitochondrial energization in hepatoma cells: a comparison with oxidative burst. Cancer Res. 1993;53:2676–2682.
    1. Cao Z., Xia Z., Zhou Y., Yang X., Hao H., Peng N. Methylcrotonoyl-CoA carboxylase 1 potentiates RLR-induced NF-kappaB signaling by targeting MAVS complex. Sci. Rep. 2016;6:33557.
    1. Mills E.L., Kelly B., O'Neill L.A.J. Mitochondria are the powerhouses of immunity. Nat. Immunol. 2017;18:488–498.
    1. Pearce E.L., Pearce E.J. Metabolic pathways in immune cell activation and quiescence. Immunity. 2013;38:633–643.
    1. Wu D., Sanin D.E., Everts B., Chen Q., Qiu J., Buck M.D. Type 1 interferons induce changes in core metabolism that are critical for immune function. Immunity. 2016;44:1325–1336.
    1. Ten Garcia-Sastre A. Strategies of interferon evasion by viruses. Cell Host Microbe. 2017;22:176–184.
    1. West A.P., Shadel G.S. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat. Rev. Immunol. 2017;17:363–375.
    1. Cossarizza A., Pinti M., Nasi M., Gibellini L., Manzini S., Roat E. Increased plasma levels of extracellular mitochondrial DNA during HIV infection: a new role for mitochondrial damage-associated molecular patterns during inflammation. Mitochondrion. 2011;11:750–755.
    1. Zhang Q., Raoof M., Chen Y., Sumi Y., Sursal T., Junger W. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–107.
    1. Kung C.T., Hsiao S.Y., Tsai T.C., Su C.M., Chang W.N., Huang C.R. Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room. J. Transl. Med. 2012;10:130.
    1. Nakahira K., Kyung S.Y., Rogers A.J., Gazourian L., Youn S., Massaro A.F. Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: derivation and validation. PLoS Med. 2013;10 e1001577; discussion e1001577.
    1. Lai J.H., Wang M.Y., Huang C.Y., Wu C.H., Hung L.F., Yang C.Y. Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells. EMBO Rep. 2018;19
    1. Hotz M.J., Qing D., Shashaty M.G.S., Zhang P., Faust H., Sondheimer N. Red blood cells homeostatically bind mitochondrial DNA through TLR9 to maintain quiescence and to prevent lung injury. Am. J. Respir. Crit. Care Med. 2018;197:470–480.
    1. Dhanwani R., Takahashi M., Sharma S. Cytosolic sensing of immuno-stimulatory DNA, the enemy within. Curr. Opin. Immunol. 2018;50:82–87.
    1. Aguirre S., Luthra P., Sanchez-Aparicio M.T., Maestre A.M., Patel J., Lamothe F. Dengue virus NS2B protein targets cGAS for degradation and prevents mitochondrial DNA sensing during infection. Nat. Microbiol. 2017;2:17037.
    1. Aguirre S., Fernandez-Sesma A. Collateral damage during dengue virus infection: making sense of DNA by cGAS. J. Virol. 2017;91(14) doi: 10.1128/JVI.01081-16.
    1. Luo X., Hong L., Cheng C., Li N., Zhao X., Shi F. DNMT1 mediates metabolic reprogramming induced by Epstein-Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma. Cell Death Dis. 2018;9:619.
    1. Tillo D., Ray S., Syed K.S., Gaylor M.R., He X., Wang J. The Epstein-Barr virus B-ZIP protein Zta recognizes specific DNA sequences containing 5-methylcytosine and 5-hydroxymethylcytosine. Biochemistry. 2017;56:6200–6210.
    1. Wiedmer A., Wang P., Zhou J., Rennekamp A.J., Tiranti V., Zeviani M. Epstein-Barr virus immediate-early protein Zta co-opts mitochondrial single-stranded DNA binding protein to promote viral and inhibit mitochondrial DNA replication. J. Virol. 2008;82:4647–4655.
    1. Corcoran J.A., Saffran H.A., Duguay B.A., Smiley J.R. Herpes simplex virus UL12.5 targets mitochondria through a mitochondrial localization sequence proximal to the N terminus. J. Virol. 2009;83:2601–2610.
    1. Moren C., Gonzalez-Casacuberta I., Alvarez-Fernandez C., Bano M., Catalan-Garcia M., Guitart-Mampel M. HIV-1 promonocytic and lymphoid cell lines: an in vitro model of in vivo mitochondrial and apoptotic lesion. J. Cell Mol. Med. 2017;21:402–409.
    1. Duguay B.A., Saffran H.A., Ponomarev A., Duley S.A., Eaton H.E., Smiley J.R. Elimination of mitochondrial DNA is not required for herpes simplex virus 1 replication. J. Virol. 2014;88:2967–2976.
    1. Chen H., Chomyn A., Chan D.C. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J. Biol. Chem. 2005;280:26185–26192.
    1. Buck M.D., O'Sullivan D., Klein Geltink R.I., Curtis J.D., Chang C.H., Sanin D.E. Mitochondrial dynamics controls T cell fate through metabolic programming. Cell. 2016;166:63–76.
    1. Khan M., Syed G.H., Kim S.J., Siddiqui A. Mitochondrial dynamics and viral infections: a close nexus. Biochim. Biophys. Acta, Mol. Cell. Biol. Lipids. 2015;1853:2822–2833.
    1. Kim S.J., Khan M., Quan J., Till A., Subramani S., Siddiqui A. Hepatitis B virus disrupts mitochondrial dynamics: induces fission and mitophagy to attenuate apoptosis. PLoS Pathog. 2013;9
    1. Pal A.D., Basak N.P., Banerjee A.S., Banerjee S. Epstein-Barr virus latent membrane protein-2A alters mitochondrial dynamics promoting cellular migration mediated by Notch signaling pathway. Carcinogenesis. 2014;35:1592–1601.
    1. McCormick A.L., Smith V.L., Chow D., Mocarski E.S. Disruption of mitochondrial networks by the human cytomegalovirus UL37 gene product viral mitochondrion-localized inhibitor of apoptosis. J. Virol. 2003;77:631–641.
    1. Shi C.S., Qi H.Y., Boularan C., Huang N.N., Abu-Asab M., Shelhamer J.H. SARS-coronavirus open reading frame-9b suppresses innate immunity by targeting mitochondria and the MAVS/TRAF3/TRAF6 signalosome. J. Immunol. 2014;193:3080–3089.
    1. Yu C.Y., Liang J.J., Li J.K., Lee Y.L., Chang B.L., Su C.I. Dengue virus impairs mitochondrial fusion by cleaving mitofusins. PLoS Pathog. 2015;11
    1. Chatel-Chaix L., Cortese M., Romero-Brey I., Bender S., Neufeldt C.J., Fischl W. Dengue virus perturbs mitochondrial morphodynamics to dampen innate immune responses. Cell Host Microbe. 2016;20:342–356.
    1. Dikic I., Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat. Rev. Mol. Cell Biol. 2018;19(6):349–364. doi: 10.1038/s41580-018-0003-4.
    1. Stolz A., Ernst A., Dikic I. Cargo recognition and trafficking in selective autophagy. Nat. Cell Biol. 2014;16:495–501.
    1. Orsini M., Morceau F., Dicato M., Diederich M. Autophagy as a pharmacological target in hematopoiesis and hematological disorders. Biochem. Pharmacol. 2018;152:347–361. doi: 10.1016/j.bcp.2018.04.007.
    1. Ding B., Zhang L., Li Z., Zhong Y., Tang Q., Qin Y. The matrix protein of human parainfluenza virus type 3 induces mitophagy that suppresses interferon responses. Cell Host Microbe. 2017;21(538–547)
    1. Li M., Li J., Yang J., Liu J., Zhang Z., Song X. Respiratory syncytial virus replication is promoted by autophagy-mediated inhibition of apoptosis. J. Virol. 2018;92(8) doi: 10.1128/JVI.02193-17.
    1. Xia M., Gonzalez P., Li C., Meng G., Jiang A., Wang H. Mitophagy enhances oncolytic measles virus replication by mitigating DDX58/RIG-I-like receptor signaling. J. Virol. 2014;88:5152–5164.
    1. Lupfer C., Thomas P.G., Anand P.K., Vogel P., Milasta S., Martinez J. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat. Immunol. 2013;14:480–488.
    1. Sin J., McIntyre L., Stotland A., Feuer R., Gottlieb R.A. Coxsackievirus B escapes the infected cell in ejected mitophagosomes. J. Virol. 2017;91(24) doi: 10.1128/JVI.01347-17.
    1. Raj K., Berguerand S., Southern S., Doorbar J., Beard P. E1 empty set E4 protein of human papillomavirus type 16 associates with mitochondria. J. Virol. 2004;78:7199–7207.
    1. Huang C.Y., Chiang S.F., Lin T.Y., Chiou S.H., Chow K.C. HIV-1 Vpr triggers mitochondrial destruction by impairing Mfn2-mediated ER-mitochondria interaction. PLoS ONE. 2012;7
    1. Halestrap A.P., Brenner C. The adenine nucleotide translocase: a central component of the mitochondrial permeability transition pore and key player in cell death. Curr. Med. Chem. 2003;10:1507–1525.
    1. Roggero R., Robert-Hebmann V., Harrington S., Roland J., Vergne L., Jaleco S. Binding of human immunodeficiency virus type 1 gp120 to CXCR4 induces mitochondrial transmembrane depolarization and cytochrome c-mediated apoptosis independently of Fas signaling. J. Virol. 2001;75:7637–7650.
    1. D'Agostino D.M., Silic-Benussi M., Hiraragi H., Lairmore M.D., Ciminale V. The human T-cell leukemia virus type 1 p13II protein: effects on mitochondrial function and cell growth. Cell Death Differ. 2005;12(Suppl. 1):905–915.
    1. Wasilenko S.T., Stewart T.L., Meyers A.F., Barry M. Vaccinia virus encodes a previously uncharacterized mitochondrial-associated inhibitor of apoptosis. Proc. Natl. Acad. Sci. U.S.A. 2003;100:14345–14350.
    1. Arnoult D., Bartle L.M., Skaletskaya A., Poncet D., Zamzami N., Park P.U. Cytomegalovirus cell death suppressor vMIA blocks Bax- but not Bak-mediated apoptosis by binding and sequestering Bax at mitochondria. Proc. Natl. Acad. Sci. U.S.A. 2004;101:7988–7993.
    1. Sarid R., Sato T., Bohenzky R.A., Russo J.J., Chang Y. Kaposi’s sarcoma-associated herpesvirus encodes a functional bcl-2 homologue. Nat. Med. 1997;3:293–298.
    1. Cai Q., Guo Y., Xiao B., Banerjee S., Saha A., Lu J. Epstein-Barr virus nuclear antigen 3C stabilizes Gemin3 to block p53-mediated apoptosis. PLoS Pathog. 2011;7
    1. Burwitz B.J., Malouli D., Bimber B.N., Reed J.S., Ventura A.B., Hancock M.H. Cross-species rhesus cytomegalovirus infection of cynomolgus macaques. PLoS Pathog. 2016;12
    1. Martensson C.U., Doan K.N., Becker T. Effects of lipids on mitochondrial functions. Biochim. Biophys. Acta, Mol. Cell. Biol. Lipids. 2017;1862:102–113.
    1. Kameoka S., Adachi Y., Okamoto K., Iijima M., Sesaki H. Phosphatidic acid and cardiolipin coordinate mitochondrial dynamics. Trends Cell Biol. 2018;28:67–76.
    1. Iyer S.S., He Q., Janczy J.R., Elliott E.I., Zhong Z., Olivier A.K. Mitochondrial cardiolipin is required for Nlrp3 inflammasome activation. Immunity. 2013;39:311–323.
    1. Shen Z., Li Y., Gasparski A.N., Abeliovich H., Greenberg M.L. Cardiolipin regulates mitophagy through the protein kinase C pathway. J. Biol. Chem. 2017;292:2916–2923.
    1. Hwang K.Y., Choi Y.B. Modulation of mitochondrial antiviral signaling by human herpesvirus 8 interferon regulatory factor 1. J. Virol. 2016;90:506–520.
    1. Martinez V., Diemert M.C., Braibant M., Potard V., Charuel J.L., Barin F. Anticardiolipin antibodies in HIV infection are independently associated with antibodies to the membrane proximal external region of gp41 and with cell-associated HIV DNA and immune activation. Clin. Infect. Dis. 2009;48:123–132.
    1. He Z., Zhu X., Wen W., Yuan J., Hu Y., Chen J. Dengue virus subverts host innate immunity by targeting adaptor protein MAVS. J. Virol. 2016;90:7219–7230.
    1. Varga Z.T., Grant A., Manicassamy B., Palese P. Influenza virus protein PB1-F2 inhibits the induction of type I interferon by binding to MAVS and decreasing mitochondrial membrane potential. J. Virol. 2012;86:8359–8366.
    1. Yoshizumi T., Ichinohe T., Sasaki O., Otera H., Kawabata S., Mihara K. Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity. Nat. Commun. 2014;5:4713.
    1. Li X.D., Sun L., Seth R.B., Pineda G., Chen Z.J. Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. Proc. Natl. Acad. Sci. U.S.A. 2005;102:17717–17722.
    1. Hiscott J., Lacoste J., Lin R. Recruitment of an interferon molecular signaling complex to the mitochondrial membrane: disruption by hepatitis C virus NS3-4A protease. Biochem. Pharmacol. 2006;72:1477–1484.
    1. Li Y., Song W., Wu J., Zhang Q., He J., Li A. MAVS-mediated host cell defense is inhibited by Borna disease virus. Int. J. Biochem. Cell Biol. 2013;45:1546–1555.
    1. Xu L., Xiao N., Liu F., Ren H., Gu J. Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria. Proc. Natl. Acad. Sci. U.S.A. 2009;106:1530–1535.
    1. You F., Sun H., Zhou X., Sun W., Liang S., Zhai Z. PCBP2 mediates degradation of the adaptor MAVS via the HECT ubiquitin ligase AIP4. Nat. Immunol. 2009;10:1300–1308.
    1. Zhou X., You F., Chen H., Jiang Z. Poly(C)-binding protein 1 (PCBP1) mediates housekeeping degradation of mitochondrial antiviral signaling (MAVS) Cell Res. 2012;22:717–727.
    1. Wei C., Ni C., Song T., Liu Y., Yang X., Zheng Z. The hepatitis B virus X protein disrupts innate immunity by downregulating mitochondrial antiviral signaling protein. J. Immunol. 2010;185:1158–1168.
    1. Lai J.H., Lin Y.L., Hsieh S.L. Pharmacological intervention for dengue virus infection. Biochem. Pharmacol. 2017;129:14–25.
    1. Hong X., Kim E.S., Guo H. Epigenetic regulation of hepatitis B virus covalently closed circular DNA: implications for epigenetic therapy against chronic hepatitis B. Hepatology. 2017;66:2066–2077.
    1. Tsai K.N., Kuo C.F., Ou J.J. Mechanisms of hepatitis B virus persistence. Trends Microbiol. 2018;26:33–42.
    1. Moos W.H., Pinkert C.A., Irwin M.H., Faller D.V., Kodukula K., Glavas I.P. Epigenetic treatment of persistent viral infections. Drug Dev. Res. 2017;78:24–36.
    1. Gane E.J., Weilert F., Orr D.W., Keogh G.F., Gibson M., Lockhart M.M. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int. 2010;30:1019–1026.
    1. Wnek M., Ressel L., Ricci E., Rodriguez-Martinez C., Guerrero J.C., Ismail Z. Herpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro study. Acta Neuropathol. 2016;132:433–451.
    1. Quarato G., D'Aprile A., Gavillet B., Vuagniaux G., Moradpour D., Capitanio N. The cyclophilin inhibitor alisporivir prevents hepatitis C virus-mediated mitochondrial dysfunction. Hepatology. 2012;55:1333–1343.
    1. Quarato G., Scrima R., Ripoli M., Agriesti F., Moradpour D., Capitanio N. Protective role of amantadine in mitochondrial dysfunction and oxidative stress mediated by hepatitis C virus protein expression. Biochem. Pharmacol. 2014;89:545–556.
    1. Kim S.J., Jang J.Y., Kim E.J., Cho E.K., Ahn D.G., Kim C. Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation. Hepatology. 2017;66:758–771.
    1. Williams G.S., Boyman L., Chikando A.C., Khairallah R.J., Lederer W.J. Mitochondrial calcium uptake. Proc. Natl. Acad. Sci. U.S.A. 2013;110:10479–10486.
    1. Dong Z., Shanmughapriya S., Tomar D., Siddiqui N., Lynch S., Nemani N. Mitochondrial Ca(2+) uniporter is a mitochondrial luminal redox sensor that augments MCU channel activity. Mol. Cell. 2017;65(6):1014–1028.e7. doi: 10.1016/j.molcel.2017.01.032.
    1. Bouchard M.J., Wang L.H., Schneider R.J. Calcium signaling by HBx protein in hepatitis B virus DNA replication. Science. 2001;294:2376–2378.
    1. Bouchard M.J., Puro R.J., Wang L., Schneider R.J. Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication. J. Virol. 2003;77:7713–7719.
    1. Kim S.J., Ahn D.G., Syed G.H., Siddiqui A. The essential role of mitochondrial dynamics in antiviral immunity. Mitochondrion. 2018;41:21–27.
    1. Twig G., Elorza A., Molina A.J., Mohamed H., Wikstrom J.D., Walzer G. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27:433–446.
    1. Kim S.J., Syed G.H., Khan M., Chiu W.W., Sohail M.A., Gish R.G. Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence. Proc. Natl. Acad. Sci. U.S.A. 2014;111:6413–6418.
    1. Nakahira K., Haspel J.A., Rathinam V.A., Lee S.J., Dolinay T., Lam H.C. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat. Immunol. 2011;12:222–230.
    1. Shimada K., Crother T.R., Karlin J., Dagvadorj J., Chiba N., Chen S. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401–414.
    1. Huang X.Y., Li D., Chen Z.X., Huang Y.H., Gao W.Y., Zheng B.Y. Hepatitis B Virus X protein elevates Parkin-mediated mitophagy through Lon Peptidase in starvation. Exp. Cell Res. 2018;368:75–83.
    1. Lin M.T., Beal M.F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443:787–795.
    1. Wang B., Nie J., Wu L., Hu Y., Wen Z., Dong L. AMPKalpha2 protects against the development of heart failure by enhancing mitophagy via PINK1 phosphorylation. Circ. Res. 2018;122:712–729.
    1. Carroll R.G., Hollville E., Martin S.J. Parkin sensitizes toward apoptosis induced by mitochondrial depolarization through promoting degradation of Mcl-1. Cell Rep. 2014;9:1538–1553.
    1. Morigi M., Perico L., Rota C., Longaretti L., Conti S., Rottoli D. Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury. J. Clin. Invest. 2015;125:715–726.
    1. Wang Q., Zhang M., Torres G., Wu S., Ouyang C., Xie Z. Metformin suppresses diabetes-accelerated atherosclerosis via the inhibition of Drp1-mediated mitochondrial fission. Diabetes. 2017;66:193–205.

Source: PubMed

3
Abonnere