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Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia

In-vitro studies with different Fanconi anemia (FA) cell lines and FANC gene silenced cell lines indicating involvement of mitochondria function in pathogenesis of FA have been reported. However, in-vivo studies have not been studied so far to understand the role of mitochondrial markers in pathogen...

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Autores principales: Solanki, Avani, Rajendran, Aruna, Mohan, Sheila, Raj, Revathy, Vundinti, Babu Rao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961948/
https://www.ncbi.nlm.nih.gov/pubmed/31940411
http://dx.doi.org/10.1371/journal.pone.0227603
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author Solanki, Avani
Rajendran, Aruna
Mohan, Sheila
Raj, Revathy
Vundinti, Babu Rao
author_facet Solanki, Avani
Rajendran, Aruna
Mohan, Sheila
Raj, Revathy
Vundinti, Babu Rao
author_sort Solanki, Avani
collection PubMed
description In-vitro studies with different Fanconi anemia (FA) cell lines and FANC gene silenced cell lines indicating involvement of mitochondria function in pathogenesis of FA have been reported. However, in-vivo studies have not been studied so far to understand the role of mitochondrial markers in pathogenesis of FA. We have carried out a systematic set of biomarker studies for elucidating involvement of mitochondrial dysfunction in disease pathogenesis for Indian FA patients. We report changes in the mtDNA number in 59% of FA patients studied, a high frequency of mtDNA variations (37.5% of non-synonymous variations and 62.5% synonymous variations) and downregulation of mtDNA complex-I and complex-III encoding genes of OXPHOS (p<0.05) as strong biomarkers for impairment of mitochondrial functions in FA. Deregulation of expression of mitophagy genes (ATG; p>0.05, Beclin-1; p>0.05, and MAP1-LC3, p<0.05) has also been observed, suggesting inability of FA cells to clear off impaired mitochondria. We hypothesize that accumulation of such impaired mitochondria in FA cells therefore may be the principal cause for bone marrow failure (BMF) and a plausible effect of inefficient clearance of impaired mitochondria in FA.
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spelling pubmed-69619482020-01-26 Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia Solanki, Avani Rajendran, Aruna Mohan, Sheila Raj, Revathy Vundinti, Babu Rao PLoS One Research Article In-vitro studies with different Fanconi anemia (FA) cell lines and FANC gene silenced cell lines indicating involvement of mitochondria function in pathogenesis of FA have been reported. However, in-vivo studies have not been studied so far to understand the role of mitochondrial markers in pathogenesis of FA. We have carried out a systematic set of biomarker studies for elucidating involvement of mitochondrial dysfunction in disease pathogenesis for Indian FA patients. We report changes in the mtDNA number in 59% of FA patients studied, a high frequency of mtDNA variations (37.5% of non-synonymous variations and 62.5% synonymous variations) and downregulation of mtDNA complex-I and complex-III encoding genes of OXPHOS (p<0.05) as strong biomarkers for impairment of mitochondrial functions in FA. Deregulation of expression of mitophagy genes (ATG; p>0.05, Beclin-1; p>0.05, and MAP1-LC3, p<0.05) has also been observed, suggesting inability of FA cells to clear off impaired mitochondria. We hypothesize that accumulation of such impaired mitochondria in FA cells therefore may be the principal cause for bone marrow failure (BMF) and a plausible effect of inefficient clearance of impaired mitochondria in FA. Public Library of Science 2020-01-15 /pmc/articles/PMC6961948/ /pubmed/31940411 http://dx.doi.org/10.1371/journal.pone.0227603 Text en © 2020 Solanki et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Solanki, Avani
Rajendran, Aruna
Mohan, Sheila
Raj, Revathy
Vundinti, Babu Rao
Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia
title Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia
title_full Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia
title_fullStr Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia
title_full_unstemmed Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia
title_short Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia
title_sort mitochondrial dna variations and mitochondrial dysfunction in fanconi anemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961948/
https://www.ncbi.nlm.nih.gov/pubmed/31940411
http://dx.doi.org/10.1371/journal.pone.0227603
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