Oncotarget

Research Papers:

Impaired mitophagy in Fanconi anemia is dependent on mitochondrial fission

Pavithra Shyamsunder, Milan Esner, Maunish Barvalia, Yu Jun Wu, Tomáš Loja, Huat Bay Boon, Matilde E. Lleonart, Rama S Verma, Lumir Krejci and Alex Lyakhovich _

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Oncotarget. 2016; 7:58065-58074. https://doi.org/10.18632/oncotarget.11161

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Abstract

Pavithra Shyamsunder1,2,*, Milan Esner3,*, Maunish Barvalia4,10, Yu Jun Wu5, Tomáš Loja6, Huat Bay Boon5, Matilde E. Lleonart7, Rama S Verma2, Lumir Krejci8,9, Alex Lyakhovich8,9

1Cancer Science Institute of Singapore, National University of Singapore, Singapore

2Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India

3Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

4Indian Institute of Technology Madras, Chennai, India

5Yong Loo Lin School of Medicine, Department of Anatomy, National University of Singapore, Singapore

6Central European Institute of Technology, Masaryk University, Brno, Czech Republic

7Translational Research in Cancer Stem Cells, Vall d´Hebron Institut de Recerca (VHIR), Barcelona, Spain

8Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic

9ICRC- FNUSA, International Clinical Research Center and St. Anne’s University Hospital Brno, Brno, Czech Republic

10Current Address: Department of Microbiology and Immunology, University of British Columbia, Life Sciences Institute, Vancouver, British Columbia, Canada

*These authors have contributed equally to this work

Correspondence to:

Alex Lyakhovich, email: [email protected], [email protected]

Lumir Krejci, email: [email protected]

Keywords: mitophagy, impaired autophagy, Fanconi anemia, ROS, oxidative stress

Received: June 04, 2016     Accepted: July 29, 2016     Published: August 09, 2016

ABSTRACT

Fanconi anemia (FA) is a rare genetic disorder associated with bone-marrow failure, genome instability and cancer predisposition. Recently, we and others have demonstrated dysfunctional mitochondria with morphological alterations in FA cells accompanied by high reactive oxygen species (ROS) levels. Mitochondrial morphology is regulated by continuous fusion and fission events and the misbalance between these two is often accompanied by autophagy. Here, we provide evidence of impaired autophagy in FA. We demonstrate that FA cells have increased number of autophagic (presumably mitophagic) events and accumulate dysfunctional mitochondria due to an impaired ability to degrade them. Moreover, mitochondrial fission accompanied by oxidative stress (OS) is a prerequisite condition for mitophagy in FA and blocking this pathway may release autophagic machinery to clear dysfunctional mitochondria.


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