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Assessment of tRNAThr and tRNAGln Variants and Mitochondrial Functionality in Parkinson’s Disease (PD) Patients of Tamil Nadu Population

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Abstract

Parkinson’s disease (PD) is speculated with genetic and environmental factors. At molecular level, the mitochondrial impact is stated to be one of the causative reasons for PD. In this study, we investigated the mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and adenosine triphosphate (ATP) levels along with mitochondrial tRNA alterations among three age categories of PD. By determining the genetic and organellar functionality using molecular techniques, the ROS levels were reported to be high with decreased MMP and ATP in the late-onset age group than in other two age categories. Likewise, the tRNA significancy in tRNAThr and tRNAGln was noticed with C4335T and G15927A mutations in late-onset and early-onset PD groups respectively. Therefore, from the findings, ageing has shown a disruption in tRNA metabolism leading to critical functioning of ATP synthesis and MMP, causing oxidative stress in PD patients. These physiological outcomes show that ageing has a keen role in the divergence of mitochondrial function, thereby proving a correlation with ageing and maintenance of mitochondrial homeostasis in PD.

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References

  • Angelova PR, Horrocks MH, Klenerman D et al (2015) Lipid peroxidation is essential for α-synuclein-induced cell death. Journal of neurochemistry 133:582–589

    Article  PubMed  PubMed Central  Google Scholar 

  • Bingol B, Sheng M (2016) Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond. Free Radical Biology and Medicine 100:210–222

    Article  PubMed  Google Scholar 

  • Cassarino DS, Fall CP, Swerdlow RH et al (1997) Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson’s disease. Biochim Biophys Acta (BBA) Mol Basis Dis 1362:77–89

    Article  Google Scholar 

  • Cossarizza A, Baccaranicontri M, Kalashnikova G, Franceschi C (1993) A new method for the cytofluorometric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1). Biochemical and biophysical research communications 197:40–45

    Article  PubMed  Google Scholar 

  • Darzynkiewicz Z, Bedner E, Smolewski P (2001) Flow cytometry in analysis of cell cycle and apoptosis. Elsevier, pp 179–193

  • Egensperger R, Kösel S, Schnopp NM et al (1997) Association of the mitochondrial tRNA(A4336G) mutation with Alzheimer’s and Parkinson’s diseases. Neuropathol Appl Neurobiol 23:315–321

    Article  PubMed  Google Scholar 

  • Gandhi S, Wood-Kaczmar A, Yao Z et al (2009) PINK1-associated Parkinson’s disease is caused by neuronal vulnerability to calcium-induced cell death. Mol Cell 33:627–638. https://doi.org/10.1016/j.molcel.2009.02.013

    Article  PubMed  PubMed Central  Google Scholar 

  • Garone C, Pietra A, Nesci S (2022) From the structural and (Dys) function of ATP synthase to deficiency in age-related diseases. Life (Basel) 12. https://doi.org/10.3390/life12030401

  • Hällberg BM, Larsson N-G (2014) Making proteins in the powerhouse. Cell Metab 20:226–240. https://doi.org/10.1016/j.cmet.2014.07.001

    Article  PubMed  Google Scholar 

  • Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300. https://doi.org/10.1093/geronj/11.3.298

    Article  PubMed  Google Scholar 

  • Helley MP, Pinnell J, Sportelli C, Tieu K (2017) Mitochondria: a common target for genetic mutations and environmental toxicants in Parkinson’s disease. Front Genet 8:177

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang H, Chen J, Lu H et al (2017) Iron-induced generation of mitochondrial ROS depends on AMPK activity. Biometals 30:623–628. https://doi.org/10.1007/s10534-017-0023-0

    Article  PubMed  Google Scholar 

  • Hutchin T, Cortopassi G (1995) A mitochondrial DNA clone is associated with increased risk for Alzheimer disease. Proc Natl Acad Sci 92:6892–6895

    Article  PubMed  PubMed Central  Google Scholar 

  • Je G, Kim Y-S (2017) Mitochondrial ROS-mediated post-transcriptional regulation of α-synuclein through miR-7 and miR-153. Neurosci Lett 661:132–136. https://doi.org/10.1016/j.neulet.2017.09.065

    Article  PubMed  Google Scholar 

  • Jiang H, Liu L, Sun DL et al (2016) Interaction between passive smoking and folic acid supplement during pregnancy on autism spectrum disorder behaviors in children aged 3 years. Zhonghua Liu Xing Bing Xue Za Zhi 37:940–944. https://doi.org/10.3760/cma.j.issn.0254-6450.2016.07.007

    Article  PubMed  Google Scholar 

  • Junn E, Mouradian MM (2002) Human α-synuclein over-expression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci Lett 320:146–150

    Article  PubMed  Google Scholar 

  • Kroemer G, Zamzami N, Susin SA (1997) Mitochondrial control of apoptosis. Immunol Today 18:44–51

    Article  PubMed  Google Scholar 

  • Ludtmann MH, Angelova PR, Horrocks MH et al (2018) α-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson’s disease. Nat Commun 9:2293

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma KY, Fokkens MR, Reggiori F, Mari M, Verbeek DS (2021) Parkinson’s disease–associated VPS35 mutant reduces mitochondrial membrane potential and impairs PINK1/Parkin-mediated mitophagy. Transl Neurodegener 10(1):1–7

    Article  Google Scholar 

  • Magee R, Londin E, Rigoutsos I (2019) TRNA-derived fragments as sex-dependent circulating candidate biomarkers for Parkinson’s disease. Parkinsonism Relat Disord 65:203–209. https://doi.org/10.1016/j.parkreldis.2019.05.035

    Article  PubMed  Google Scholar 

  • Mahalaxmi I, Subramaniam MD, Gopalakrishnan AV, Vellingiri B (2021) Dysfunction in mitochondrial electron transport chain complex I, pyruvate dehydrogenase activity, and mutations in ND1 and ND4 gene in autism spectrum disorder subjects from Tamil Nadu Population, India. Mol Neurobiol 58:5303–5311. https://doi.org/10.1007/s12035-021-02492-w

    Article  PubMed  Google Scholar 

  • Mayr-Wohlfart U, Paulus C, Henneberg A, Rödel G (1996) Mitochondrial DNA mutations in multiple sclerosis patients with severe optic involvement. Acta Neurol Scand 94:167–171. https://doi.org/10.1111/j.1600-0404.1996.tb07048.x

    Article  PubMed  Google Scholar 

  • Mayr-Wohlfart U, Rödel G, Henneberg A (1997) Mitochondrial tRNA (Gln) and tRNA(Thr) gene variants in Parkinson’s disease. Eur J Med Res 2:111–113

    PubMed  Google Scholar 

  • Nicholls DG (2004) Mitochondrial membrane potential and aging. Aging Cell 3:35–40. https://doi.org/10.1111/j.1474-9728.2003.00079.x

    Article  PubMed  Google Scholar 

  • Paldor I, Madrer N, Vaknine Treidel S et al (2023) Cerebrospinal fluid and blood profiles of transfer RNA fragments show age, sex and Parkinson’s disease-related changes. J Neurochem 164:671–83

    Article  PubMed  Google Scholar 

  • Panel M, Ghaleh B, Morin D (2018) Mitochondria and ageing: a role for the mitochondrial transition pore? Ageing Cell 17:e12793

    Article  Google Scholar 

  • Qadri R, Goyal V, Behari M et al (2021) Alteration of mitochondrial function in oxidative stress in parkinsonian neurodegeneration: a cross-sectional study. Ann Indian Acad Neurol 24:506

    Article  PubMed  PubMed Central  Google Scholar 

  • Qadri R, Namdeo M, Behari M et al (2018) Alterations in mitochondrial membrane potential in peripheral blood mononuclear cells in Parkinson’s disease: potential for a novel biomarker. Restor Neurol Neurosci 36:719–727. https://doi.org/10.3233/RNN-180852

    Article  PubMed  Google Scholar 

  • Ricci J-E, Muñoz-Pinedo C, Fitzgerald P et al (2004) Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain. Cell 117:773–786

    Article  PubMed  Google Scholar 

  • Richter G, Sonnenschein A, Grünewald T et al (2002) Novel mitochondrial DNA mutations in Parkinson’s disease. J Neural Transm 109:721–729

    Article  PubMed  Google Scholar 

  • Salvioli S, Ardizzoni A, Franceschi C, Cossarizza A (1997) JC-1, but not DiOC6 (3) or rhodamine 123, is a reliable fluorescent probe to assess ΔΨ changes in intact cells: implications for studies on mitochondrial functionality during apoptosis. FEBS Lett 411:77–82

    Article  PubMed  Google Scholar 

  • Shoffner JM, Brown MD, Torroni A et al (1993) Mitochondrial DNA variants observed in Alzheimer disease and Parkinson disease patients. Genomics 17:171–184. https://doi.org/10.1006/geno.1993.1299

    Article  PubMed  Google Scholar 

  • Simon DK, Mayeux R, Marder K et al (2000) Mitochondrial DNA mutations in complex I and tRNA genes in Parkinson’s disease. Neurology 54:703–709. https://doi.org/10.1212/wnl.54.3.703

    Article  PubMed  Google Scholar 

  • Suski JM, Lebiedzinska M, Bonora M et al (2012) Relation between mitochondrial membrane potential and ROS formation. Mitochondrial bioenergetics: methods and protocols 183–205

  • Vellingiri B, Suriyanarayanan A, Selvaraj P et al (2022a) Role of heavy metals (copper (Cu), arsenic (As), cadmium (Cd), iron (Fe) and lithium (Li)) induced neurotoxicity. Chemosphere 134625

  • Vellingiri B, Chandrasekhar M, Sabari SS et al (2022b) Neurotoxicity of pesticides–a link to neurodegeneration. Ecotoxicol Environ Saf 243:113972

    Article  PubMed  Google Scholar 

  • Vellingiri B, Suriyanarayanan A, Abraham KS et al (2022c) Influence of heavy metals in Parkinson’s disease: an overview. J Neurolo 1–14

  • Vellingiri B, Kiruthika B, Mahalaxmi I et al (2023) Role of telomeres and telomerase in Parkinson’s disease - a new theranostics? Adv Biol 2300097

  • Venkatesan D, Iyer M, Narayanasamy A et al (2022) Genotypic-phenotypic analysis, metabolic profiling and clinical correlations in Parkinson’s disease patients from Tamil Nadu population, India. J Mol Neurosci 1–14

  • Venkatesan D, Iyer M, Wilson R et al (2021) The association between multiple risk factors, clinical correlations and molecular insights in Parkinson’s disease patients from Tamil Nadu population, India. Neurosci Lett 755:135903

    Article  PubMed  Google Scholar 

  • Wallace DC (1994) Mitochondrial DNA sequence variation in human evolution and disease. Proc Natl Acad Sci 91:8739–8746

    Article  PubMed  PubMed Central  Google Scholar 

  • Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407. https://doi.org/10.1146/annurev.genet.39.110304.095751

    Article  PubMed  PubMed Central  Google Scholar 

  • Yoon KL, Aprille JR, Ernst SG (1991) Mitochondrial tRNA(thr) mutation in fatal infantile respiratory enzyme deficiency. Biochem Biophys Res Commun 176:1112–1115. https://doi.org/10.1016/0006-291x(91)90399-r

    Article  PubMed  Google Scholar 

  • Zhou Z, Sun B, Yu D, Bian M (2021) Roles of tRNA metabolism in aging and lifespan. Cell Death Dis 12:548. https://doi.org/10.1038/s41419-021-03838-x

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank Indian Council of Medical Research (ICMR) [grant number: 45/2/2018-Hum/BMS], Government of India and Bharathiar University, Coimbatore to carry out this research work. Also, I would like to thank Karpagam Academy of Higher Education (Deemed to be University), Coimbatore 641021, India, for the revision of the manuscript.

Funding

This work was supported by the Indian Council of Medical Research [grant number: 45/2/2018-Hum/BMS], Government of India.

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Authors and Affiliations

  1. Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, 641 046, Tamil Nadu, India

    Dhivya Venkatesan, Neethu Raj & Balachandar Vellingiri

  2. Centre for Neuroscience, Department of Biotechnology, Karpagam Academy of Higher Education (Deemed to be University), Coimbatore, 641021, India

    Dhivya Venkatesan & Mahalaxmi Iyer

  3. Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, 632 014, India

    Abilash Valsala Gopalakrishnan

  4. Disease Proteomics Laboratory, Department of Zoology, Bharathiar University, Coimbatore, 641 046, Tamil Nadu, India

    Arul Narayanasamy

  5. Department of Biotechnology, Mizoram University, Aizawl, Mizoram, 796004, India

    Nachimuthu Senthil Kumar

  6. Human Cytogenetics and Stem Cell Laboratory, Department of Zoology, School of Basic Sciences, Central University of Punjab, Bathinda, Punjab, 151401, India

    Balachandar Vellingiri

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  1. Dhivya Venkatesan
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Dhivya Venkatesan, Mahalaxmi Iyer, and Neethu Raj. The first draft of the manuscript was written by Dhivya Venkatesan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Balachandar Vellingiri.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Bharathiar University (BUHEC-0014/2018; dated: 10.08.2018)

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Informed consent was obtained from all individual participants included in the study.

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Venkatesan, D., Iyer, M., Raj, N. et al. Assessment of tRNAThr and tRNAGln Variants and Mitochondrial Functionality in Parkinson’s Disease (PD) Patients of Tamil Nadu Population. J Mol Neurosci 73, 912–920 (2023). https://doi.org/10.1007/s12031-023-02154-7

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