In search for mitochondrial biomarkers of Parkinson's disease: Findings in parkin-mutant human fibroblasts.

Autor: Kamienieva I; Nencki Institute of Experimental Biology, Polish Academy of Sciences, ul. Pasteura 3, 02-093 Warszawa, Poland., Charzyńska A; Nencki Institute of Experimental Biology, Polish Academy of Sciences, ul. Pasteura 3, 02-093 Warszawa, Poland., Duszyński J; Nencki Institute of Experimental Biology, Polish Academy of Sciences, ul. Pasteura 3, 02-093 Warszawa, Poland., Malińska D; Nencki Institute of Experimental Biology, Polish Academy of Sciences, ul. Pasteura 3, 02-093 Warszawa, Poland. Electronic address: d.malinska@nencki.edu.pl., Szczepanowska J; Nencki Institute of Experimental Biology, Polish Academy of Sciences, ul. Pasteura 3, 02-093 Warszawa, Poland. Electronic address: j.szczepanowska@nencki.edu.pl.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2023 Oct; Vol. 1869 (7), pp. 166787. Date of Electronic Publication: 2023 Jun 10.
DOI: 10.1016/j.bbadis.2023.166787
Abstrakt: Most cases of Parkinson's disease (PD) are idiopathic, with unknown aetiology and genetic background. However, approximately 10 % of cases are caused by defined genetic mutations, among which mutations in the parkin gene are the most common. There is increasing evidence of the involvement of mitochondrial dysfunction in the development of both idiopathic and genetic PD. However, the data on mitochondrial changes reported by different studies are inconsistent, which can reflect the variability in genetic background of the disease. Mitochondria, as a plastic and dynamic organelles, are the first place in the cell to respond to external and internal stress. In this work, we characterized mitochondrial function and dynamics (network morphology and turnover regulation) in primary fibroblasts from PD patients with parkin mutations. We performed clustering analysis of the obtained data to compare the profiles of mitochondrial parameters in PD patients and healthy donors. This allowed to extract the features characteristic for PD patients fibroblasts, which were a smaller and less complex mitochondrial network and decreased levels of mitochondrial biogenesis regulators and mitophagy mediators. The approach we used allowed a comprehensive characteristics of elements common for mitochondrial dynamics remodelling accompanying pathogenic mutation. This may be helpful in the deciphering key pathomechanisms of the PD disease.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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