Impaired mitophagy in Fanconi anemia is dependent on mitochondrial fission
| Autor: | Pavithra Shyamsunder, Maunish Barvalia, Alex Lyakhovich, Lumir Krejci, Yu Jun Wu, Milan Ešner, Huat Bay Boon, Rama Shanker Verma, Matilde E. Lleonart, Tomáš Loja |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Autolysosome Mitochondrial Degradation Mitochondrion Mitochondrial Dynamics Cell Line 03 medical and health sciences DNM1L Rare Diseases 0302 clinical medicine Microscopy Electron Transmission Mitophagy Autophagy Humans Medicine impaired autophagy business.industry ROS Mitochondria Cell biology Oxidative Stress Fanconi Anemia 030104 developmental biology Microscopy Fluorescence Oncology Mitochondrial biogenesis 030220 oncology & carcinogenesis Mitochondrial fission Reactive Oxygen Species business Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.11161 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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