title: Impaired mitophagy in Fanconi anemia is dependent on mitochondrial fission.
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.
authors: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
authors: Pavithra
authors: P
authors: Shyamsunder
authors: Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors: Milan
authors: M
authors: Esner
authors: Indian Institute of Technology Madras, Chennai, India.|Current Address: Department of Microbiology and Immunology, University of British Columbia, Life Sciences Institute, Vancouver, British Columbia, Canada.
authors: Maunish
authors: M
authors: Barvalia
authors: Yong Loo Lin School of Medicine, Department of Anatomy, National University of Singapore, Singapore.
authors: Yu Jun
authors: YJ
authors: Wu
authors: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors: Tomáš
authors: T
authors: Loja
authors: Yong Loo Lin School of Medicine, Department of Anatomy, National University of Singapore, Singapore.
authors: Huat Bay
authors: HB
authors: Boon
authors: Translational Research in Cancer Stem Cells, Vall d´Hebron Institut de Recerca (VHIR), Barcelona, Spain.
authors: Matilde E
authors: ME
authors: Lleonart
authors: Stem Cell and Molecular Biology Laboratory, Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India.
authors: Rama S
authors: RS
authors: Verma
authors: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|ICRC- FNUSA, International Clinical Research Center and St. Anne's University Hospital Brno, Brno, Czech Republic.
authors: Lumir
authors: L
authors: Krejci
authors: Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.|ICRC- FNUSA, International Clinical Research Center and St. Anne's University Hospital Brno, Brno, Czech Republic.
authors: Alex
authors: A
authors: Lyakhovich
mesh_terms: D001343:Autophagy; D002460:Cell Line; D005199:Fanconi Anemia / Q000503:physiopathology*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D063306:Mitophagy; D018384:Oxidative Stress; D035583:Rare Diseases / Q000503:physiopathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: Fanconi anemia; ROS; impaired autophagy; mitophagy; oxidative stress