Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia.
Adolescent
Adult
Autophagy-Related Protein 12
/ genetics
Autophagy-Related Protein 8 Family
/ genetics
Beclin-1
/ genetics
Case-Control Studies
Cell Line
Child
DNA, Mitochondrial
/ genetics
Fanconi Anemia
/ genetics
Female
Genetic Variation
/ genetics
Humans
India
Male
Mitochondria
/ genetics
Mitophagy
Reactive Oxygen Species
/ metabolism
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
26
06
2019
accepted:
23
12
2019
entrez:
16
1
2020
pubmed:
16
1
2020
medline:
14
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31940411
doi: 10.1371/journal.pone.0227603
pii: PONE-D-19-17987
pmc: PMC6961948
doi:
Substances chimiques
ATG12 protein, human
0
Autophagy-Related Protein 12
0
Autophagy-Related Protein 8 Family
0
Beclin-1
0
DNA, Mitochondrial
0
GABARAPL2 protein, human
0
Reactive Oxygen Species
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0227603Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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