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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Perspective

Mitophagy and Neuroinflammation: A Compelling Interplay

Author(s): Nikolaos Charmpilas, Evandro Fei Fang and Konstantinos Palikaras*

Volume 21, Issue 7, 2023

Published on: 13 March, 2023

Page: [1477 - 1481] Pages: 5

DOI: 10.2174/1570159X20666220628153632

Price: $65

Abstract

Mitochondria are the main sites of energy production and a major source of metabolic stress. Not surprisingly, impairment of mitochondrial homeostasis is strongly associated with the development and progression of a broad spectrum of human pathologies, including neurodegenerative disorders. Mitophagy mediates the selective degradation of damaged organelles, thus promoting cellular viability and tissue integrity. Defective mitophagy triggers cellular senescence and prolonged neuroinflammation, leading eventually to cell death and brain homeostasis collapse. Here, we survey the intricate interplay between mitophagy and neuroinflammation, highlighting that mitophagy can be a focal point for therapeutic interventions to tackle neurodegeneration.

Keywords: Ageing, energy homeostasis, immunity, inflammation, metabolism, mitochondria, mitophagy, neurodegeneration

Graphical Abstract

[1]
Palikaras, K.; Lionaki, E.; Tavernarakis, N. Mechanisms of mitophagy in cellular homeostasis, physiology and pathology. Nat. Cell Biol., 2018, 20(9), 1013-1022.
[http://dx.doi.org/10.1038/s41556-018-0176-2] [PMID: 30154567]
[2]
Killackey, S.A.; Philpott, D.J.; Girardin, S.E. Mitophagy pathways in health and disease. J. Cell Biol., 2020, 219(11), e202004029.
[http://dx.doi.org/10.1083/jcb.202004029] [PMID: 32926082]
[3]
Narendra, D.P.; Jin, S.M.; Tanaka, A.; Suen, D.F.; Gautier, C.A.; Shen, J.; Cookson, M.R.; Youle, R.J. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol., 2010, 8(1), e1000298.
[http://dx.doi.org/10.1371/journal.pbio.1000298] [PMID: 20126261]
[4]
Koyano, F.; Okatsu, K.; Kosako, H.; Tamura, Y.; Go, E.; Kimura, M.; Kimura, Y.; Tsuchiya, H.; Yoshihara, H.; Hirokawa, T.; Endo, T.; Fon, E.A.; Trempe, J.F.; Saeki, Y.; Tanaka, K.; Matsuda, N. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature, 2014, 510(7503), 162-166.
[http://dx.doi.org/10.1038/nature13392] [PMID: 24784582]
[5]
Sarraf, S.A.; Raman, M.; Guarani-Pereira, V.; Sowa, M.E.; Huttlin, E.L.; Gygi, S.P.; Harper, J.W. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature, 2013, 496(7445), 372-376.
[http://dx.doi.org/10.1038/nature12043] [PMID: 23503661]
[6]
Sandoval, H.; Thiagarajan, P.; Dasgupta, S.K.; Schumacher, A.; Prchal, J.T.; Chen, M.; Wang, J. Essential role for Nix in autophagic maturation of erythroid cells. Nature, 2008, 454(7201), 232-235.
[http://dx.doi.org/10.1038/nature07006] [PMID: 18454133]
[7]
Schweers, R.L.; Zhang, J.; Randall, M.S.; Loyd, M.R.; Li, W.; Dorsey, F.C.; Kundu, M.; Opferman, J.T.; Cleveland, J.L.; Miller, J.L.; Ney, P.A. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc. Natl. Acad. Sci. USA, 2007, 104(49), 19500-19505.
[http://dx.doi.org/10.1073/pnas.0708818104] [PMID: 18048346]
[8]
Quinsay, M.N.; Thomas, R.L.; Lee, Y.; Gustafsson, A.B. Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore. Autophagy, 2010, 6(7), 855-862.
[http://dx.doi.org/10.4161/auto.6.7.13005] [PMID: 20668412]
[9]
Liu, L.; Feng, D.; Chen, G.; Chen, M.; Zheng, Q.; Song, P.; Ma, Q.; Zhu, C.; Wang, R.; Qi, W.; Huang, L.; Xue, P.; Li, B.; Wang, X.; Jin, H.; Wang, J.; Yang, F.; Liu, P.; Zhu, Y.; Sui, S.; Chen, Q. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat. Cell Biol., 2012, 14(2), 177-185.
[http://dx.doi.org/10.1038/ncb2422] [PMID: 22267086]
[10]
Chu, C.T.; Ji, J.; Dagda, R.K.; Jiang, J.F.; Tyurina, Y.Y.; Kapralov, A.A.; Tyurin, V.A.; Yanamala, N.; Shrivastava, I.H.; Mohammadyani, D.; Wang, K.Z.Q.; Zhu, J.; Klein-Seetharaman, J.; Balasubramanian, K.; Amoscato, A.A.; Borisenko, G.; Huang, Z.; Gusdon, A.M.; Cheikhi, A.; Steer, E.K.; Wang, R.; Baty, C.; Watkins, S.; Bahar, I.; Bayir, H.; Kagan, V.E. Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nat. Cell Biol., 2013, 15(10), 1197-1205.
[http://dx.doi.org/10.1038/ncb2837] [PMID: 24036476]
[11]
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(7), 2916-2923.
[http://dx.doi.org/10.1074/jbc.M116.753574] [PMID: 28062576]
[12]
Wei, Y.; Chiang, W.C.; Sumpter, R., Jr; Mishra, P.; Levine, B. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell, 2017, 168(1-2), 224-238.e10.
[http://dx.doi.org/10.1016/j.cell.2016.11.042] [PMID: 28017329]
[13]
Han, S.; Jeong, Y.Y.; Sheshadri, P.; Su, X.; Cai, Q. Mitophagy regulates integrity of mitochondria at synapses and is critical for synaptic maintenance. EMBO Rep., 2020, 21(9), e49801.
[http://dx.doi.org/10.15252/embr.201949801] [PMID: 32627320]
[14]
Sun, N.; Yun, J.; Liu, J.; Malide, D.; Liu, C.; Rovira, I.I.; Holmström, K.M.; Fergusson, M.M.; Yoo, Y.H.; Combs, C.A.; Finkel, T. Measuring in vivo mitophagy. Mol. Cell, 2015, 60(4), 685-696.
[http://dx.doi.org/10.1016/j.molcel.2015.10.009] [PMID: 26549682]
[15]
Swerdlow, N.S.; Wilkins, H.M. Mitophagy and the Brain. Int. J. Mol. Sci., 2020, 21(24), E9661.
[http://dx.doi.org/10.3390/ijms21249661] [PMID: 33352896]
[16]
Fang, E.F.; Hou, Y.; Palikaras, K.; Adriaanse, B.A.; Kerr, J.S.; Yang, B.; Lautrup, S.; Hasan-Olive, M.M.; Caponio, D.; Dan, X.; Rocktäschel, P.; Croteau, D.L.; Akbari, M.; Greig, N.H.; Fladby, T.; Nilsen, H.; Cader, M.Z.; Mattson, M.P.; Tavernarakis, N.; Bohr, V.A. Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease. Nat. Neurosci., 2019, 22(3), 401-412.
[http://dx.doi.org/10.1038/s41593-018-0332-9] [PMID: 30742114]
[17]
Xie, C.; Zhuang, X.X.; Niu, Z.; Ai, R.; Lautrup, S.; Zheng, S.; Jiang, Y.; Han, R.; Gupta, T.S.; Cao, S.; Lagartos-Donate, M.J.; Cai, C.Z.; Xie, L.M.; Caponio, D.; Wang, W.W.; Schmauck-Medina, T.; Zhang, J.; Wang, H.L.; Lou, G.; Xiao, X.; Zheng, W.; Palikaras, K.; Yang, G.; Caldwell, K.A.; Caldwell, G.A.; Shen, H.M.; Nilsen, H.; Lu, J.H.; Fang, E.F. Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow. Nat. Biomed. Eng., 2022, 6(1), 76-93.
[http://dx.doi.org/10.1038/s41551-021-00819-5] [PMID: 34992270]
[18]
Park, H.; Chung, K.M.; An, H.K.; Gim, J.E.; Hong, J.; Woo, H.; Cho, B.; Moon, C.; Yu, S.W. Parkin promotes mitophagic cell death in adult hippocampal neural stem cells following insulin withdrawal. Front. Mol. Neurosci., 2019, 12, 46.
[http://dx.doi.org/10.3389/fnmol.2019.00046] [PMID: 30853892]
[19]
Zaninello, M.; Palikaras, K.; Naon, D.; Iwata, K.; Herkenne, S.; Quintana-Cabrera, R.; Semenzato, M.; Grespi, F.; Ross-Cisneros, F.N.; Carelli, V.; Sadun, A.A.; Tavernarakis, N.; Scorrano, L. Inhibition of autophagy curtails visual loss in a model of autosomal dominant optic atrophy. Nat. Commun., 2020, 11(1), 4029.
[http://dx.doi.org/10.1038/s41467-020-17821-1] [PMID: 32788597]
[20]
Zaninello, M.; Palikaras, K.; Sotiriou, A.; Tavernarakis, N.; Scorrano, L. Sustained intracellular calcium rise mediates neuronal mitophagy in models of autosomal dominant optic atrophy. Cell Death Differ., 2022, 29(1), 167-177.
[http://dx.doi.org/10.1038/s41418-021-00847-3] [PMID: 34389813]
[21]
Patergnani, S.; Bonora, M.; Ingusci, S.; Previati, M.; Marchi, S.; Zucchini, S.; Perrone, M.; Wieckowski, M.R.; Castellazzi, M.; Pugliatti, M.; Giorgi, C.; Simonato, M.; Pinton, P. Antipsychotic drugs counteract autophagy and mitophagy in multiple sclerosis. Proc. Natl. Acad. Sci. USA, 2021, 118(24), e2020078118.
[http://dx.doi.org/10.1073/pnas.2020078118] [PMID: 34099564]
[22]
DiSabato, D.J.; Quan, N.; Godbout, J.P. Neuroinflammation: The devil is in the details. J. Neurochem., 2016, 139(Suppl. 2), 136-153.
[http://dx.doi.org/10.1111/jnc.13607] [PMID: 26990767]
[23]
Leng, F.; Edison, P. Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here? Nat. Rev. Neurol., 2021, 17(3), 157-172.
[http://dx.doi.org/10.1038/s41582-020-00435-y] [PMID: 33318676]
[24]
Mills, E.L.; Kelly, B.; O’Neill, L.A.J. Mitochondria are the powerhouses of immunity. Nat. Immunol., 2017, 18(5), 488-498.
[http://dx.doi.org/10.1038/ni.3704] [PMID: 28418387]
[25]
Buskiewicz, I.A.; Montgomery, T.; Yasewicz, E.C.; Huber, S.A.; Murphy, M.P.; Hartley, R.C.; Kelly, R.; Crow, M.K.; Perl, A.; Budd, R.C.; Koenig, A. Reactive oxygen species induce virus-independent MAVS oligomerization in systemic lupus erythematosus. Sci. Signal., 2016, 9(456), ra115.
[http://dx.doi.org/10.1126/scisignal.aaf1933] [PMID: 27899525]
[26]
Tigano, M.; Vargas, D.C.; Tremblay-Belzile, S.; Fu, Y.; Sfeir, A. Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance. Nature, 2021, 591(7850), 477-481.
[http://dx.doi.org/10.1038/s41586-021-03269-w] [PMID: 33627873]
[27]
Zhong, Z.; Umemura, A.; Sanchez-Lopez, E.; Liang, S.; Shalapour, S.; Wong, J.; He, F.; Boassa, D.; Perkins, G.; Ali, S.R.; McGeough, M.D.; Ellisman, M.H.; Seki, E.; Gustafsson, A.B.; Hoffman, H.M.; Diaz-Meco, M.T.; Moscat, J.; Karin, M. NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell, 2016, 164(5), 896-910.
[http://dx.doi.org/10.1016/j.cell.2015.12.057] [PMID: 26919428]
[28]
Goldberg, M.S.; Fleming, S.M.; Palacino, J.J.; Cepeda, C.; Lam, H.A.; Bhatnagar, A.; Meloni, E.G.; Wu, N.; Ackerson, L.C.; Klapstein, G.J.; Gajendiran, M.; Roth, B.L.; Chesselet, M.F.; Maidment, N.T.; Levine, M.S.; Shen, J. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J. Biol. Chem., 2003, 278(44), 43628-43635.
[http://dx.doi.org/10.1074/jbc.M308947200] [PMID: 12930822]
[29]
Perez, F.A.; Palmiter, R.D. Parkin-deficient mice are not a robust model of parkinsonism. Proc. Natl. Acad. Sci. USA, 2005, 102(6), 2174-2179.
[http://dx.doi.org/10.1073/pnas.0409598102] [PMID: 15684050]
[30]
Kitada, T.; Pisani, A.; Porter, D.R.; Yamaguchi, H.; Tscherter, A.; Martella, G.; Bonsi, P.; Zhang, C.; Pothos, E.N.; Shen, J. Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc. Natl. Acad. Sci. USA, 2007, 104(27), 11441-11446.
[http://dx.doi.org/10.1073/pnas.0702717104] [PMID: 17563363]
[31]
Sliter, D.A.; Martinez, J.; Hao, L.; Chen, X.; Sun, N.; Fischer, T.D.; Burman, J.L.; Li, Y.; Zhang, Z.; Narendra, D.P.; Cai, H.; Borsche, M.; Klein, C.; Youle, R.J. Parkin and PINK1 mitigate STING-induced inflammation. Nature, 2018, 561(7722), 258-262.
[http://dx.doi.org/10.1038/s41586-018-0448-9] [PMID: 30135585]
[32]
Kim, J.; Byun, J.W.; Choi, I.; Kim, B.; Jeong, H.K.; Jou, I.; Joe, E. PINK1 deficiency enhances inflammatory cytokine release from acutely prepared brain slices. Exp. Neurobiol., 2013, 22(1), 38-44.
[http://dx.doi.org/10.5607/en.2013.22.1.38] [PMID: 23585721]
[33]
Mouton-Liger, F.; Rosazza, T.; Sepulveda-Diaz, J.; Ieang, A.; Hassoun, S.M.; Claire, E.; Mangone, G.; Brice, A.; Michel, P.P.; Corvol, J.C.; Corti, O. Parkin deficiency modulates NLRP3 inflammasome activation by attenuating an A20-dependent negative feedback loop. Glia, 2018, 66(8), 1736-1751.
[http://dx.doi.org/10.1002/glia.23337] [PMID: 29665074]
[34]
Yunfu, W.; Guangjian, L.; Ping, Z.; Yanpeng, S.; Xiaoxia, F.; Wei, H.; Jiang, Y.; Jingquan, H.; Songlin, W.; Hongyan, Z.; Yong, L.; Shi, C. PINK1 and its familial Parkinson’s disease-associated mutation regulate brain vascular endothelial inflammation. J. Mol. Neurosci., 2014, 53(1), 109-116.
[http://dx.doi.org/10.1007/s12031-013-0207-1] [PMID: 24385196]
[35]
Hou, Y.; Wei, Y.; Lautrup, S.; Yang, B.; Wang, Y.; Cordonnier, S.; Mattson, M.P.; Croteau, D.L.; Bohr, V.A. NAD+ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer’s disease via cGAS-STING. Proc. Natl. Acad. Sci. USA, 2021, 118(37), e2011226118.
[http://dx.doi.org/10.1073/pnas.2011226118] [PMID: 34497121]
[36]
Paul, B.D.; Snyder, S.H.; Bohr, V.A. Signaling by cGAS-STING in neurodegeneration, neuroinflammation, and aging. Trends Neurosci., 2021, 44(2), 83-96.
[http://dx.doi.org/10.1016/j.tins.2020.10.008] [PMID: 33187730]
[37]
Yang, B.; Dan, X.; Hou, Y.; Lee, J.H.; Wechter, N.; Krishnamurthy, S.; Kimura, R.; Babbar, M.; Demarest, T.; McDevitt, R.; Zhang, S.; Zhang, Y.; Mattson, M.P.; Croteau, D.L.; Bohr, V.A. NAD+ supplementation prevents STING-induced senescence in ataxia telangiectasia by improving mitophagy. Aging Cell, 2021, 20(4), e13329.
[http://dx.doi.org/10.1111/acel.13329] [PMID: 33734555]
[38]
Palikaras, K.; Lionaki, E.; Tavernarakis, N. Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans. Nature, 2015, 521(7553), 525-528.
[http://dx.doi.org/10.1038/nature14300] [PMID: 25896323]
[39]
McWilliams, T.G.; Prescott, A.R.; Allen, G.F.; Tamjar, J.; Munson, M.J.; Thomson, C.; Muqit, M.M.; Ganley, I.G. mito-QC illuminates mitophagy and mitochondrial architecture in vivo. J. Cell Biol., 2016, 214(3), 333-345.
[http://dx.doi.org/10.1083/jcb.201603039] [PMID: 27458135]
[40]
Wrighton, P.J.; Shwartz, A.; Heo, J.M.; Quenzer, E.D.; LaBella, K.A.; Harper, J.W.; Goessling, W. Quantitative intravital imaging in zebrafish reveals in vivo dynamics of physiological-stress-induced mitophagy. J. Cell Sci., 2021, 134(4), jcs256255.
[http://dx.doi.org/10.1242/jcs.256255] [PMID: 33536245]
[41]
Rosado, C.J.; Mijaljica, D.; Hatzinisiriou, I.; Prescott, M.; Devenish, R.J. Rosella: A fluorescent pH-biosensor for reporting vacuolar turnover of cytosol and organelles in yeast. Autophagy, 2008, 4(2), 205-213.
[http://dx.doi.org/10.4161/auto.5331] [PMID: 18094608]

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