Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia
Avani Solanki1, Aruna Rajendran2, Sheila Mohan3
1Department of Cytogenetics, National Institute of Immunohaematology, K.E.M. Hospital Campus, Parel, Mumbai, Maharashtra, India.
Plos One
|January 16, 2020
Summary
Mitochondrial dysfunction is implicated in Fanconi anemia (FA) pathogenesis. Impaired mitochondria accumulation, due to inefficient clearance, may cause bone marrow failure in FA patients.
Area of Science:
- Biochemistry
- Genetics
- Cell Biology
Background:
- In-vitro studies suggest mitochondrial dysfunction in Fanconi anemia (FA) pathogenesis.
- In-vivo studies are lacking to confirm the role of mitochondrial markers in FA.
Purpose of the Study:
- To investigate mitochondrial dysfunction biomarkers in Indian FA patients.
- To elucidate the role of mitochondrial markers in FA pathogenesis.
Main Methods:
- Biomarker studies on Indian FA patients.
- Analysis of mtDNA number and variations.
- Gene expression analysis of OXPHOS and mitophagy genes.
Main Results:
- 59% of FA patients showed altered mtDNA number.
- High frequency of mtDNA variations (37.5% non-synonymous, 62.5% synonymous).
- Downregulation of OXPHOS complex-I and III genes (p<0.05).
- Deregulation of mitophagy genes (ATG, Beclin-1, MAP1-LC3; p<0.05).
Conclusions:
- Mitochondrial dysfunction is evident in FA patients.
- Impaired mitochondria accumulation, due to inefficient clearance, may cause bone marrow failure in FA.
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