Mitochondrial DNA variations and mitochondrial dysfunction in Fanconi anemia

Autoři: Avani Solanki aff001;  Aruna Rajendran aff002;  Sheila Mohan aff003;  Revathy Raj aff003;  Babu Rao Vundinti aff001
Působiště autorů: Department of Cytogenetics, National Institute of Immunohaematology, K.E.M. Hospital Campus, Parel, Mumbai, Maharashtra, India aff001;  Department of Hematology, Institute of Child Health and Hospital for Children, Egmore, Chennai, Tamil Nadu, India aff002;  Pediatric Haematology Department, Apollo Children’s Hospital, Chennai, Tamil Nadu, India aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: 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.

Klíčová slova:

Blood – Complement system – Gene expression – Immunoblotting – Mitochondria – Mitochondrial DNA – Mutation – Pathogenesis


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2020 Číslo 1
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