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Review

PINK1-PRKN mediated mitophagy: differences between in vitro and in vivo models

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Pages 1396-1405 | Received 05 Jun 2022, Accepted 18 Oct 2022, Published online: 03 Nov 2022

References

  • Spinelli JB, Haigis MC. The multifaceted contributions of mitochondria to cellular metabolism. Nat Cell Biol. 2018;20(7):745–754.
  • Nguyen TN, Padman BS, Lazarou M. Deciphering the molecular signals of PINK1/parkin mitophagy. Trends Cell Biol. 2016;26(10):733–744.
  • Keeney PM, Xie J, Capaldi RA, et al. Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci. 2006;26(19):5256–5264.
  • Wang X. The antiapoptotic activity of melatonin in neurodegenerative diseases. CNS Neurosci Ther. 2009;15(4):345–357.
  • Panov AV, Gutekunst C-A, Leavitt BR, et al. Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat Neurosci. 2002;5(8):731–736.
  • Lin MT, Beal MF. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 2006;443(7113):787–795.
  • Chao H, Lin C, Zuo Q, et al. Cardiolipin-dependent mitophagy guides outcome after traumatic brain injury. J Neurosci. 2019;39(10):1930–1943.
  • Teresak P, Lapao A, Subic N, et al. Regulation of PRKN-independent mitophagy. Autophagy. 2022;18(1):24–39.
  • Lees AJ, Hardy J, Revesz T. Parkinson’s disease. Lancet. 2009;373(9680):2055–2066.
  • Bloem BR, Okun MS, Klein C. Parkinson’s disease. Lancet. 2021;397(10291):2284–2303.
  • Langston JW. Epidemiology versus genetics in Parkinson’s disease: progress in resolving an age-old debate. Ann Neurol. 1998;44(3 Suppl 1):S45–52.
  • Javitch JA, D’Amato RJ, Strittmatter SM, et al. Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6 -tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci U S A. 1985;82(7):2173–2177.
  • Nicklas WJ, Vyas I, Heikkila RE. Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenyl-pyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. Life Sci. 1985;36(26):2503–2508.
  • Ramsay RR, Singer TP. Energy-dependent uptake of N-methyl-4-phenylpyridinium, the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, by mitochondria. J Biol Chem. 1986;261(17):7585–7587.
  • Liou HH, Tsai MC, Chen CJ, et al. Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology. 1997;48(6):1583–1588.
  • Tanner CM, Kamel F, Ross GW, et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect. 2011;119(6):866–872.
  • Betarbet R, Sherer TB, MacKenzie G, et al. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci. 2000;3(12):1301–1306.
  • Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease. Lancet. 1989;1(8649):1269.
  • Schapira AH, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem. 1990;54(3):823–827.
  • Giannoccaro MP, La Morgia C, Rizzo G, et al. Mitochondrial DNA and primary mitochondrial dysfunction in P arkinson’s disease. Mov Disord. 2017;32(3):346–363.
  • Dolle C, Flønes I, Nido GS, et al. Defective mitochondrial DNA homeostasis in the substantia nigra in Parkinson disease. Nat Commun. 2016;7(1):13548.
  • Toulorge D, Schapira AH, Hajj R. Molecular changes in the postmortem parkinsonian brain. J Neurochem. 2016;139 Suppl 1:27–58.
  • McInerney-Leo A, Hadley DW, Gwinn-Hardy K, et al. Genetic testing in Parkinson’s disease. Mov Disord. 2005;20(1):1–10.
  • Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson’s disease. Neuron. 2015;85(2):257–273.
  • Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304(5674):1158–1160.
  • Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392(6676):605–608.
  • Greene JC, Whitworth AJ, Kuo I, et al. Mitochondrial pathology and apoptotic muscle degeneration in Drosophila parkin mutants. Proc Natl Acad Sci U S A. 2003;100(7):4078–4083.
  • Clark IE, Dodson MW, Jiang C, et al. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006;441(7097):1162–1166.
  • Park J, Lee SB, Lee S, et al. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006;441(7097):1157–1161.
  • Liu Y, Guardia-Laguarta C, Yin J, et al. The ubiquitination of PINK1 is restricted to its mature 52-kDa form. Cell Rep. 2017;20(1):30–39.
  • Rub C, Wilkening A, Voos W. Mitochondrial quality control by the Pink1/Parkin system. Cell Tissue Res. 2017;367(1):111–123.
  • Arena G, Valente EM. PINK1 in the limelight: multiple functions of an eclectic protein in human health and disease. J Pathol. 2017;241(2):251–263.
  • Kane LA, Lazarou M, Fogel AI, et al. PINK1 phosphorylates ubiquitin to activate Parkin E3 ubiquitin ligase activity. J Cell Biol. 2014;205(2):143–153.
  • Seirafi M, Kozlov G, Gehring K. Parkin structure and function. FEBS J. 2015;282(11):2076–2088.
  • Chaugule VK, Burchell L, Barber KR, et al. Autoregulation of Parkin activity through its ubiquitin-like domain. EMBO J. 2011;30(14):2853–2867.
  • Riley BE, Lougheed JC, Callaway K, et al. Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases. Nat Commun. 2013;4(1):1982.
  • Spratt DE, Julio Martinez-Torres R, Noh YJ, et al. A molecular explanation for the recessive nature of parkin-linked Parkinson’s disease. Nat Commun. 2013;4(1):1983.
  • Trempe JF, Sauvé V, Grenier K, et al. Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science. 2013;340(6139):1451–1455.
  • Wauer T, Komander D. Structure of the human Parkin ligase domain in an autoinhibited state. EMBO J. 2013;32(15):2099–2112.
  • Ordureau A, Sarraf S, Duda D, et al. Quantitative proteomics reveal a feedforward mechanism for mitochondrial PARKIN translocation and ubiquitin chain synthesis. Mol Cell. 2014;56(3):360–375.
  • Narendra D, Kane LA, Hauser DN, et al. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy. 2010;6(8):1090–1106.
  • Wong YC, Holzbaur EL. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci U S A. 2014;111(42):E4439–48.
  • Geisler S, Holmström KM, Skujat D, et al. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol. 2010;12(2):119–131.
  • Lazarou M, Sliter DA, Kane LA, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524(7565):309–314.
  • Sarraf SA, Raman M, Guarani-Pereira V, et al. Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization. Nature. 2013;496(7445):372–376.
  • Chan NC, Chan DC. Parkin uses the UPS to ship off dysfunctional mitochondria. Autophagy. 2011;7(7):771–772.
  • Vives-Bauza C, Przedborski S. PINK1 points Parkin to mitochondria. Autophagy. 2010;6(5):674–675.
  • Narendra D, Tanaka A, Suen D-F, et al. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008;183(5):795–803.
  • Matsuda N, Sato S, Shiba K, et al. PINK1 stabilized by mitochondrial depolarization recruits Parkin to damaged mitochondria and activates latent Parkin for mitophagy. J Cell Biol. 2010;189(2):211–221.
  • Narendra DP, Youle RJ. Targeting mitochondrial dysfunction: role for PINK1 and Parkin in mitochondrial quality control. Antioxid Redox Signal. 2011;14(10):1929–1938.
  • Schubert AF, Gladkova C, Pardon E, et al. Structure of PINK1 in complex with its substrate ubiquitin. Nature. 2017;552(7683):51–56.
  • Gan ZY, Callegari S, Cobbold SA, et al. Activation mechanism of PINK1. Nature. 2022;602(7896):328–335.
  • Gautier CA, Kitada T, Shen J. Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress. Proc Natl Acad Sci U S A. 2008;105(32):11364–11369.
  • Wang X, Winter D, Ashrafi G, et al. PINK1 and Parkin target Miro for phosphorylation and degradation to arrest mitochondrial motility. Cell. 2011;147(4):893–906.
  • Huang Z, Ren S, Jiang Y, et al. PINK1 and Parkin cooperatively protect neurons against constitutively active TRP channel-induced retinal degeneration in Drosophila. Cell Death Dis. 2016;7(4):e2179.
  • Huang E, Qu D, Huang T, et al. PINK1-mediated phosphorylation of LETM1 regulates mitochondrial calcium transport and protects neurons against mitochondrial stress. Nat Commun. 2017;8(1):1399.
  • Cai Q, Zakaria H, Simone A, et al. Spatial parkin translocation and degradation of damaged mitochondria via mitophagy in live cortical neurons. Curr Biol. 2012;22(6):545–552.
  • Grenier K, Kontogiannea M, Fon EA. Short mitochondrial ARF triggers Parkin/PINK1-dependent mitophagy. J Biol Chem. 2014;289(43):29519–29530.
  • Amadoro G, Corsetti V, Florenzano F, et al. Morphological and bioenergetic demands underlying the mitophagy in post-mitotic neurons: the pink-parkin pathway. Front Aging Neurosci. 2014;6:18.
  • Kann O, Kovács R. Mitochondria and neuronal activity. Am J Physiol Cell Physiol. 2007;292(2):C641–57.
  • Deng H, Dodson MW, Huang H, et al. The Parkinson’s disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila. Proc Natl Acad Sci U S A. 2008;105(38):14503–14508.
  • Park J, Lee G, Chung J. The PINK1-Parkin pathway is involved in the regulation of mitochondrial remodeling process. Biochem Biophys Res Commun. 2009;378(3):518–523.
  • Yang Y, Ouyang Y, Yang L, et al. Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery. Proc Natl Acad Sci U S A. 2008;105(19):7070–7075.
  • Gispert S, Ricciardi F, Kurz A, et al. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One. 2009;4(6):e5777.
  • Goldberg MS, Fleming SM, Palacino JJ, et al. Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons. J Biol Chem. 2003;278(44):43628–43635.
  • Dawson TM, Ko HS, Dawson VL. Genetic animal models of Parkinson’s disease. Neuron. 2010;66(5):646–661.
  • Kitada T, Tong Y, Gautier CA, et al. Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice. J Neurochem. 2009;111(3):696–702.
  • Shin JH, Ko H, Kang H, et al. Paris (ZNF746) repression of PGC-1alpha contributes to neurodegeneration in Parkinson’s disease. Cell. 2011;144(5):689–702.
  • Rezai Amin S, Gruszczynski C, Guiard BP, et al. Viral vector-mediated Cre recombinase expression in substantia nigra induces lesions of the nigrostriatal pathway associated with perturbations of dopamine-related behaviors and hallmarks of programmed cell death. J Neurochem. 2019;150(3):330–340.
  • Pickrell AM, Huang C-H, Kennedy S, et al. Endogenous parkin preserves dopaminergic substantia nigral neurons following mitochondrial DNA mutagenic stress. Neuron. 2015;87(2):371–381.
  • Haque ME, Thomas KJ, D’Souza C, et al. Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP. Proc Natl Acad Sci U S A. 2008;105(5):1716–1721.
  • Oliveras-Salva M, Tong Y, Gautier CA, et al. Alpha-synuclein-induced neurodegeneration is exacerbated in PINK1 knockout mice. Neurobiol Aging. 2014;35(11):2625–2636.
  • Matheoud D, Cannon T, Voisin A, et al. Intestinal infection triggers Parkinson’s disease-like symptoms in Pink1(-/-) mice. Nature. 2019;571(7766):565–569.
  • Dave KD, De Silva S, Sheth NP, et al. Phenotypic characterization of recessive gene knockout rat models of Parkinson’s disease. Neurobiol Dis. 2014;70:190–203.
  • de Haas R, Heltzel LCMW, Tax D, et al. To be or not to be pink(1): contradictory findings in an animal model for Parkinson’s disease. Brain Commun. 2019;1(1):fcz016.
  • McWilliams TG, Prescott AR, Montava-Garriga L, et al. Basal mitophagy occurs independently of PINK1 in mouse tissues of high metabolic demand. Cell Metab. 2018;27(2):439–449 e5.
  • Lee JJ, Sanchez-Martinez A, Martinez Zarate A, et al. Basal mitophagy is widespread in Drosophila but minimally affected by loss of Pink1 or parkin. J Cell Biol. 2018;217(5):1613–1622.
  • Liu YT, Sliter DA, Shammas MK, et al. Mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC. Autophagy. 2021;17(11):3753–3762.
  • Wrighton PJ, Shwartz A, Heo J-M, et al. Quantitative intravital imaging in zebrafish reveals in vivo dynamics of physiological-stress-induced mitophagy. J Cell Sci. 2021;134(4). DOI:10.1242/jcs.256255.
  • Kim YY, Um JH, Yoon JH, et al. Assessment of mitophagy in mt-Keima Drosophila revealed an essential role of the PINK1-Parkin pathway in mitophagy induction in vivo. FASEB J. 2019;33(9):9742–9751.
  • Cornelissen T, Vilain S, Vints K, et al. Deficiency of parkin and PINK1 impairs age-dependent mitophagy in drosophila. Elife. 2018;7:e35878.
  • McWilliams TG, Barini E, Pohjolan-Pirhonen R, et al. Phosphorylation of Parkin at serine 65 is essential for its activation in vivo. Open Biol. 2018;8(11):180108.
  • Stauch KL, Villeneuve LM, Purnell PR, et al. SWATH-MS proteome profiling data comparison of DJ-1, Parkin, and PINK1 knockout rat striatal mitochondria. Data Brief. 2016;9:589–593.
  • Zhuang N, Li L, Chen S, et al. PINK1-dependent phosphorylation of PINK1 and Parkin is essential for mitochondrial quality control. Cell Death Dis. 2016;7(12):e2501.
  • Yamada T, Dawson TM, Yanagawa T, et al. SQSTM1/p62 promotes mitochondrial ubiquitination independently of PINK1 and PRKN/parkin in mitophagy. Autophagy. 2019;15(11):2012–2018.
  • Wang X, Cao C, Huang J, et al. One-step generation of triple gene-targeted pigs using CRISPR/Cas9 system. Sci Rep. 2016;6(1):20620.
  • Zhou X, Xin J, Fan N, et al. Generation of CRISPR/Cas9-mediated gene-targeted pigs via somatic cell nuclear transfer. Cell Mol Life Sci. 2015;72(6):1175–1184.
  • Zhou H, Falkenburger BH, Schulz JB, et al. Silencing of the Pink1 gene expression by conditional RNAi does not induce dopaminergic neuron death in mice. Int J Biol Sci. 2007;3(4):242–250.
  • Yin P, Li S, Li X-J, et al. New pathogenic insights from large animal models of neurodegenerative diseases. Protein Cell. 2022;13(10):707–720.
  • Yang W, Liu Y, Tu Z, et al. CRISPR/Cas9-mediated PINK1 deletion leads to neurodegeneration in rhesus monkeys. Cell Res. 2019;29(4):334–336.
  • Chen ZZ, Wang JY, Kang Y, et al. PINK1 gene mutation by pair truncated sgRNA/Cas9-D10A in cynomolgus monkeys. Zool Res. 2021;42(4):469–477.
  • Li H, Wu S, Ma X, et al. Co-editing PINK1 and DJ-1 genes via adeno-associated virus-delivered CRISPR/Cas9 system in adult monkey brain elicits classical parkinsonian phenotype. Neurosci Bull. 2021;37(9):1271–1288.
  • Yang W, Guo X, Tu Z, et al. PINK1 kinase dysfunction triggers neurodegeneration in the primate brain without impacting mitochondrial homeostasis. Protein Cell. 2022;13(1):26–46.
  • Yang W, Li S, Li XJ. A CRISPR monkey model unravels a unique function of PINK1 in primate brains. Mol Neurodegener. 2019;14(1):17.
  • Van Laar VS, Arnold B, Cassady SJ, et al. Bioenergetics of neurons inhibit the translocation response of Parkin following rapid mitochondrial depolarization. Hum Mol Genet. 2011;20(5):927–940.
  • Rakovic A, Shurkewitsch K, Seibler P, et al. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1)-dependent ubiquitination of endogenous Parkin attenuates mitophagy: study in human primary fibroblasts and induced pluripotent stem cell-derived neurons. J Biol Chem. 2013;288(4):2223–2237.
  • Yamano K, Youle RJ. PINK1 is degraded through the N-end rule pathway. Autophagy. 2013;9(11):1758–1769.
  • Zhou C, Huang Y, Shao Y, et al. The kinase domain of mitochondrial PINK1 faces the cytoplasm. Proc Natl Acad Sci U S A. 2008;105(33):12022–12027.
  • Fedorowicz MA, Vries‐Schneider RLA, Rüb C, et al. Cytosolic cleaved PINK 1 represses Parkin translocation to mitochondria and mitophagy. EMBO Rep. 2014;15(1):86–93.
  • Qin S, Ye L, Zheng Y, et al. Cytosolic PINK1 orchestrates protein translation during proteasomal stress by phosphorylating the translation elongation factor eEF1A1. FEBS Lett. 2021;595(4):507–520.
  • Lee Y, Stevens DA, Kang S-U, et al. PINK1 primes parkin-mediated ubiquitination of paris in dopaminergic neuronal survival. Cell Rep. 2017;18(4):918–932.
  • Wang KZQ, Steer E, Otero PA, et al. PINK1 interacts with VCP/p97 and activates PKA to promote NSFL1C/p47 phosphorylation and dendritic arborization in neurons. eNeuro. 2018;5(6):ENEURO.0466–18.2018.
  • Soman SK, Tingle D, Dagda RY, et al. Cleaved PINK1 induces neuronal plasticity through PKA-mediated BDNF functional regulation. J Neurosci Res. 2021;99(9):2134–2155.
  • Gladkova C, Maslen SL, Skehel JM, et al. Mechanism of parkin activation by PINK1. Nature. 2018;559(7714):410–414.
  • Kondapalli C, Kazlauskaite A, Zhang N, et al. PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65. Open Biol. 2012;2(5):120080.
  • Blackinton JG, Anvret A, Beilina A, et al. Expression of PINK1 mRNA in human and rodent brain and in Parkinson’s disease. Brain Res. 2007;1184:10–16.
  • Yin P, Guo X, Yang W, et al. Caspase-4 mediates cytoplasmic accumulation of TDP-43 in the primate brains. Acta Neuropathol. 2019;137(6):919–937.
  • Yin P, Bai D, Deng F, et al. SQSTM1-mediated clearance of cytoplasmic mutant TARDBP/TDP-43 in the monkey brain. Autophagy. 2021;18(8):1955–1968.
  • Marquis JM, Lettenberger SE, Kelm-Nelson CA. Early-onset Parkinsonian behaviors in female Pink1-/- rats. Behav Brain Res. 2020;377:112175.

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