BECN1s, a short splice variant of BECN1, functions in mitophagy
BECN1s, a short splice variant of BECN1, functions in mitophagy
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BECN1s 是 BECN1 的短剪接变体，在线粒体自噬中发挥作用
DOI：
10.1080/15548627.2015.1100785
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发表时间：
2015-11-01
期刊：
影响因子：
13.3
通讯作者：
Wu, Mian
中科院分区：
文献类型：
--
作者：
Cheng, Bing;Xu, An;Wu, Mian
线粒体选择性自噬（mitochondrialselectiveautophagy，mitophagy）在多种生物学过程中起着关键作用，如清除受损的线粒体，从未成熟的红细胞和精子中去除线粒体。线粒体自噬缺陷与多种人类疾病相关，包括神经退行性疾病、衰老、心脏病和自身免疫性疾病。然而，线粒体自噬的机制仍不清楚。在这里，我们报告了一种新的剪接变体BECN 1/Beclin 1，BECN 1 s，这是由一种选择性剪接机制产生的表征。BECN 1 s主要与线粒体的外膜相关。与非剪接的BECN 1不同，BECN 1对于非选择性巨自噬诱导是必不可少的，BECN 1 s对于选择性自噬是不可或缺的。此外，BECN 1在饥饿和膜去极化诱导的线粒体自噬中起着重要作用。综上所述，我们的研究结果拓宽了BECN 1作为自噬重要调节因子的观点，并暗示BECN 1 s是一种特异性线粒体自噬介体。
Mitochondria selective autophagy, known as mitophagy, plays a pivotal role in several biological processes, such as elimination of the damaged mitochondria, removal of the mitochondria from immature red blood cells and sperm. The defects in mitophagy are associated with a wide spectrum of human diseases, including neurodegenerative disease, aging, cardiac disease and autoimmune disease. However, the mechanism underlying mitophagy remains largely unclear. Here, we report the characterization of a novel splice variant of BECN1/Beclin 1, BECN1s, which is produced by an alternative splicing mechanism. BECN1s is primarily associated with the outer-membrane of mitochondria. Unlike unspliced BECN1, which is essential for nonselective macroautophagy induction, BECN1s is indispensible for mitochondria-selective autophagy. Furthermore, BECN1s plays an important role in starvation- and membrane depolarization-induced mitophagy. Taken together, our findings broaden the view of BECN1 as an important regulator in autophagy, and implicate BECN1s as a specific mitophagy mediator.