Abstract
Parkinson’s disease is a neurodegenerative disorder characterized by mitochondrial dysfunction and oxidative stress. It is usually accompanied by an imbalance in mitochondrial dynamics and changes in mitochondrial morphology that are associated with impaired function. The objectives of this study were to identify the effects of rotenone, a drug known to mimic the pathophysiology of Parkinson’s disease, on mitochondrial dynamics. Additionally, this study explored the protective effects of water-soluble Coenzyme Q10 (CoQ10) against rotenone-induced cytotoxicity in murine neuronal HT22 cells. Our results demonstrate that rotenone elevates protein expression of mitochondrial fission markers, Drp1 and Fis1, and causes an increase in mitochondrial fragmentation as evidenced through mitochondrial staining and morphological analysis. Water-soluble CoQ10 prevented mitochondrial dynamic imbalance by reducing Drp1 and Fis1 protein expression to pre-rotenone levels, as well as reducing rotenone treatment-associated mitochondrial fragmentation. Hence, water-soluble CoQ10 may have therapeutic potential in treating patients with Parkinson’s disease.
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Antony PM, Diederich NJ, Krüger R, Balling R (2013) The hallmarks of Parkinson’s disease. FEBS J 280:5981–5993
Barsoum MJ, Yuan H, Gerencser AA, Liot G, Kushnareva Y, Gräber S, Kovacs I, Lee WD, Waggoner J, Cui J, White AD, Bossy B, Martinou JC, Youle RJ, Lipton SA, Ellisman MH, Perkins GA, Bossy-Wetzel E (2006) Nitric oxide-induced mitochondrial fission is regulated by dynamin-related GTPases in neurons. EMBO J 25:3900–3911
Bergamini C, Moruzzi N, Sblendido A, Lenaz G, Fato R. 2012. A water soluble CoQ10 formulation improves intracellular distribution and promotes mitochondrial respiration in cultured cells. PloS ONE 7:e33712.
Chang CR, Blackstone C (2010) Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1. Ann NY Acad Sci 1201:34–39
Deheshi S, Dabiri B, Fan S, Tsang M, Rintoul GL (2015) Changes in mitochondrial morphology induced by calcium or rotenone in primary astrocytes occur predominantly through ROS-mediated remodeling. J Neurochem 133:684–699
Gomez-Lazaro M, Bonekamp NA, Galindo MF, Jordan J, Schrader M (2008) 6-Hydroxydopamine (6-OHDA) induces Drp1-dependent mitochondrial fragmentation in SH-SY5Y cells. Free Radic Biol Med 44:1960–1969
Guo M (2012) Drosophila as a model to study mitochondrial dysfunction in Parkinson’s disease. Cold Spring Harb Perspect Med 2:A 009944
Hoppins S, Lackner L, Nunnari J (2007) The machines that divide and fuse mitochondria. Ann Rev Biochem 76:751–780
Jakobs S, Martini N, Schauss AC, Egner A, Westermann B, Hell SW (2003) Spatial and temporal dynamics of budding yeast mitochondria lacking the division component Fis1p. J Cell Sci 116:2005–2014
Ju WK, Liu Q, Kim KY, Crowston JG, Lindsey JD, Agarwal N, Ellisman MH, Perkins GA, Weinreb RN (2007) Elevated hydrostatic pressure triggers mitochondrial fission and decreases cellular ATP in differentiated RGC-5 cells. Invest Ophthalmol Vis Sci 48:2145–2151
Koopman WJ, Verkaart S, Visch HJ, Westhuizen FH, Murphy MP, Heuvel LW, Smeitink JA, Willems PH (2005) Inhibition of complex I of the electron transport chain causes O2-.-mediated mitochondrial outgrowth. Am J Physiol Cell Physiol 288:C1440–C1450
Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC (2004) Structural basis of mitochondrial tethering by mitofusin complexes. Science 305:858–862
Kumari S, Anderson L, Farmer S, Mehta SL, Li PA (2012) Hyperglycemia alters mitochondrial fission and fusion proteins in mice subjected to cerebral ischemia and reperfusion. Transl Stroke Res 3:296–304
Li H, Chen G, Ma W, Li PA (2013) Water-soluble coenzyme q10 inhibits nuclear translocation of apoptosis inducing factor and cell death caused by mitochondrial complex I inhibition. Int J Mol Sci 15:13388–133400
Mclnnes J. 2013. Insights on altered mitochondrial function and dynamics in the pathogenesis of neurodegeneration. Transl Neurodegener 2:12.
Meuer K, Suppanz IE, Lingor P, Planchamp V, Goricke B, Fichtner L, Braus GH, Dietz GP, Jakobs S, Bähr M, Weishaupt JH (2007) Cyclin dependent kinase 5 is an upstream regulator of mitochondrial fission during neuronalapoptosis. Cell Death Differ 14:651–661
Muthukumarana K, Smitha J, Jasraa H, Sikorskab M, Sandhub JK, Cohenc J, Lopatinc D, Pandeya S (2014) Genetic susceptibility model of Parkinson’s disease resulting from exposure of DJ-1 deficient mice to MPTP: evaluation of neuroprotection by Ubisol-Q10. J Parkinsons Dis 4:523–530
Ojha S, Javed H, Azimullah S, AbulKhair SB, Haque ME (2016) Glycyrrhizic acid attenuates neuron flammation and oxidative stress in rotenone model of Parkinson’s disease. Neurotox Res 29:275–287
Qin J, Wu M, Yu S, Gao X, Zhang J, Dong X, Ji J, Zhang Y, Zhou L, Zhang Q, Ding F (2015) Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson’s disease. Toxicol Lett 238:70–82
Rappold PM, Cui M, Grima JC, Fan RZ, Mesy-Bentley KL, Chen L, Zhuang X, Bowers WJ, Tieu K (2014) Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo. Nat Commun 5:5244
Santos D, Cardoso SM (2012) Mitochondrial dynamics and neuronal fate in Parkinson’s disease. Mitochondrion 12:428–437
Santos D, Esteves AR, Silva DF, Januário C, Cardoso SM (2015) The impact of mitochondrial fusion and fission modulation in sporadic Parkinson’s disease. Mol Neurobiol 52:573–586
Sarkar S, Gough B, Raymick J, Beaudoin MA, Ali SF, Virmani A, Binienda ZK (2015) Histopathological and electrophysiological indices of rotenone-evoked dopaminergic toxicity: Neuroprotective effects of acetyl-l-carnitine. Neurosci Lett 606:53–59
Schapira AH, Olanow CW, Greenamyre JT, Bezard E (2014) Slowing of neurodegeneration in Parkinson’s disease and Huntington’s disease: future therapeutic perspectives. Lancet 384:545–555
Simcox EM, Reeve A, Turnbull D (2013) Monitoring mitochondrial dynamics and complex I dysfunction in neurons: implications for Parkinson’s disease. Biochem Soc Trans 41:1618–1624
Spindler M, Beal MF, Henchcliffe C (2009) Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatr Dis Treat 5:597–610
Wang X, Su B, Liu W, He X, Gao Y, Castellani RJ, Perry G, Smith MA, Zhu X (2011) DLP1-dependent mitochondrial fragmentation mediates 1-methyl-4-phenylpyridinium toxicity in neurons: implications for Parkinson’s disease. Aging Cell 10:807–823
Youle RJ, Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337:1062–1065
Zhang Y, Chan DC. 2007. Structural basis for recruitment of mitochondrial fission complexes by Fis1. Proc Natl Acad Sci 104:18526–18530.
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This work is supported by a Grant from the National Science Foundation of China (81460179) to HNL.
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Li, HN., Zimmerman, M., Milledge, G.Z. et al. Water-Soluble Coenzyme Q10 Reduces Rotenone-Induced Mitochondrial Fission. Neurochem Res 42, 1096–1103 (2017). https://doi.org/10.1007/s11064-016-2143-2
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DOI: https://doi.org/10.1007/s11064-016-2143-2