Impaired mitophagy in Fanconi anemia is dependent on mitochondrial fission.
Impaired mitophagy in Fanconi anemia is dependent on mitochondrial fission.
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DOI：
10.18632/oncotarget.11161
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发表时间：
2016-09-06
期刊：
影响因子：
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通讯作者：
Lyakhovich A
中科院分区：
文献类型：
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作者：
Shyamsunder P;Esner M;Barvalia M;Wu YJ;Loja T;Boon HB;Lleonart ME;Verma RS;Krejci L;Lyakhovich A
范可尼贫血（FA）是一种罕见的遗传性疾病，与骨髓衰竭，基因组不稳定性和癌症易感性有关。最近，我们和其他人已经证明功能障碍的线粒体与FA细胞的形态学改变伴随着高活性氧（ROS）水平。线粒体的形态受到持续的融合和分裂事件的调节，这两者之间的失衡往往伴随着自噬。在这里，我们提供了FA中自噬受损的证据。我们证明，FA细胞有增加的自噬（大概是线粒体吞噬）事件的数量和积累功能障碍的线粒体，由于受损的能力，以降低它们。此外，线粒体分裂伴随氧化应激（OS）是FA中线粒体自噬的先决条件，阻断该途径可释放自噬机制以清除功能障碍的线粒体。
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.