Mechanisms and biology of B-cell leukemia/lymphoma 2/adenovirus E1B interacting protein 3 and Nip-like protein X.
Mechanisms and biology of B-cell leukemia/lymphoma 2/adenovirus E1B interacting protein 3 and Nip-like protein X.
复制标题
DOI：
10.1089/ars.2010.3772
复制
发表时间：
2011-04
影响因子：
6.6
通讯作者：
Ji Zhang;P. Ney
中科院分区：
文献类型：
--
作者：
Ji Zhang;P. Ney
B细胞白血病/淋巴瘤2（BCL-2）/腺病毒E1 B相互作用蛋白3（BNIP 3）和Nip样蛋白X（NIX）是非典型的BCL-2同源结构域3蛋白，参与细胞死亡，自噬和程序性线粒体清除。BNIP 3和NIX通过靶向线粒体，直接通过BCL-2相关的X蛋白或BCL-2拮抗剂/受体依赖性机制，或间接通过对内质网中钙储存的影响来引起细胞死亡。BNIP 3和NIX还通过对线粒体活性氧产生的影响或通过从与抗凋亡BCL-2家族蛋白的抑制性相互作用中释放Beclin 1来诱导自噬。BNIP 3下调缺氧细胞中的线粒体质量，而NIX是红系发育过程中线粒体消除所必需的。BNIP 3和NIX在人类健康中发挥着重要作用。由BNIP 3和NIX介导的细胞死亡与心脏病和缺血性损伤有关。癌症进展与BNIP 3的促死亡功能的丧失有关，但也与其促存活活性的诱导有关。最后，BNIP 3和NIX参与线粒体质量控制，这在衰老和退行性疾病中很重要。BNIP 3和NIX调节细胞死亡、自噬和线粒体清除的机制的阐明可能导致这些病症的治疗。
B-cell leukemia/lymphoma 2 (BCL-2)/adenovirus E1B interacting protein 3 (BNIP3) and Nip-like protein X (NIX) are atypical BCL-2 homology domain 3-only proteins involved in cell death, autophagy, and programmed mitochondrial clearance. BNIP3 and NIX cause cell death by targeting mitochondria, directly through BCL-2-associated X protein- or BCL-2-antagonist/killer-dependent mechanisms, or indirectly through an effect on calcium stores in the endoplasmic reticulum. BNIP3 and NIX also induce autophagy through an effect on mitochondrial reactive oxygen species production, or by releasing Beclin 1 from inhibitory interactions with antiapoptotic BCL-2 family proteins. BNIP3 downregulates mitochondrial mass in hypoxic cells, whereas NIX is required for mitochondrial elimination during erythroid development. BNIP3 and NIX have an emerging role in human health. Cell death mediated by BNIP3 and NIX is implicated in heart disease and ischemic injury. Cancer progression is linked to loss of the prodeath function of BNIP3, but also to induction of its prosurvival activity. Finally, BNIP3 and NIX are implicated in mitochondrial quality control, which is important in aging and degenerative disease. Elucidation of the mechanisms by which BNIP3 and NIX regulate cell death, autophagy, and mitochondrial clearance may lead to treatments for these conditions.