BNIP3L/NIX is required for elimination of mitochondria, endoplasmic reticulum and Golgi apparatus during eye lens organelle-free zone formation.
BNIP3L/NIX is required for elimination of mitochondria, endoplasmic reticulum and Golgi apparatus during eye lens organelle-free zone formation.
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DOI：
10.1016/j.exer.2018.06.003
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发表时间：
2018-09
影响因子：
3.4
通讯作者：
Kantorow M
中科院分区：
文献类型：
--
作者：
Brennan LA;McGreal-Estrada R;Logan CM;Cvekl A;Menko AS;Kantorow M
晶状体的形成和终身生长依赖于晶状体上皮细胞向晶状体纤维细胞的持续分化。为了获得成熟的结构和透明的功能，新形成的晶状体纤维细胞经历了一系列的细胞重塑事件，包括完全消除细胞器，形成晶状体细胞器无性区(OFZ)。到目前为止，晶状体纤维细胞清除细胞器的机制和要求仍未完全阐明。在以前的研究中，我们在人和鸡的晶状体中检测到自噬溶酶体中包含的线粒体的存在，这表明在OFZ形成过程中，针对线粒体的蛋白质可能需要通过有丝分裂来降解以消除线粒体。对鸡胚晶状体的高通量RNA测序一致地表明，在红细胞形成过程中针对线粒体进行消除的一种蛋白质，称为BCL2相互作用蛋白3样蛋白(BNIP3L/Nix)，在发生细胞器消除的晶状体区域达到峰值。为了探讨BNIP3L在晶状体纤维细胞重塑过程中消除线粒体的作用，我们分析了BNIP3L在新生小鼠晶状体中的表达模式，BNIP3L缺失对细胞器清除的影响以及它与晶状体细胞器的共存。我们证明了BNIP3L在小鼠晶状体中的表达模式与其在晶状体纤维细胞细胞器清除过程中对线粒体的清除起着重要作用。重要的是，我们证明了在晶状体纤维细胞重塑过程中，BNIP3L的缺失会导致线粒体的保留，令人惊讶的是，BNIP3L的缺失也会导致内质网和高尔基体的保留，但不会导致细胞核的保留。最后，我们发现BNIP3L定位于野生型新生小鼠晶状体的内质网和高尔基体，并存在于分离自成年小鼠肝脏的线粒体、内质网和高尔基体中。这些数据表明，BNIP3L是在晶状体纤维细胞重塑过程中消除线粒体、内质网和高尔基体的新需求，并提示BNIP3L在调节晶状体和非晶状体组织中的内质网和高尔基体数量方面具有新的功能。
The formation and life-long growth of the ocular lens depends on the continuous differentiation of lens epithelial cells into lens fiber cells. To achieve their mature structure and transparent function, newly formed lens fiber cells undergo a series of cellular remodeling events including the complete elimination of cellular organelles to form the lens organelle-free zone (OFZ). To date, the mechanisms and requirements for organelle elimination by lens fiber cells remain to be fully elucidated. In previous studies, we detected the presence of mitochondria contained within autophagolysosomes throughout human and chick lenses suggesting that proteins targeting mitochondria for degradation by mitophagy could be required for the elimination of mitochondria during OFZ formation. Consistently, high-throughput RNA sequencing of microdissected embryonic chick lenses revealed that expression of a protein that targets mitochondria for elimination during erythrocyte formation, called BCL2 interacting protein 3-like protein (BNIP3L/NIX), peaks in the region of lens where organelle elimination occurs. To examine the potential role for BNIP3L in the elimination of mitochondria during lens fiber cell remodeling, we analyzed the expression pattern of BNIP3L in newborn mouse lenses, the effect of its deletion on organelle elimination and its co-localization with lens organelles. We demonstrate that the expression pattern of BNIP3L in the mouse lens is consistent with it playing an important role in the elimination of mitochondria during lens fiber cell organelle elimination. Importantly, we demonstrate that deletion of BNIP3L results in retention of mitochondria during lens fiber cell remodeling, and, surprisingly, that deletion of BNIP3L also results in the retention of endoplasmic reticulum and Golgi apparatus but not nuclei. Finally, we show that BNIP3L localizes to the endoplasmic reticulum and Golgi apparatus of wild-type newborn mouse lenses and is contained within mitochondria, endoplasmic reticulum and Golgi apparatus isolated from adult mouse liver. These data identify BNIP3L as a novel requirement for the elimination of mitochondria, endoplasmic reticulum and Golgi apparatus during lens fiber cell remodeling and they suggest a novel function for BNIP3L in the regulation of endoplasmic reticulum and Golgi apparatus populations in the lens and non-lens tissues.
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影响因子：
7.8
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