Sreekumar Parameswaran G, Hinton David R, Kannan Ram
Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA, USA.
Department of Pathology and Ophthalmology, USC Roski Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Neural Regen Res. 2017 Jan;12(1):35-38. doi: 10.4103/1673-5374.198970.
In this review, the interactive mechanisms of mitochondria with the endoplasmic reticulum (ER) are discussed with emphasis on the potential protective role of the mitochondria derived peptide humanin (HN) in ER stress. The ER and mitochondria are dynamic organelles capable of modifying their structure and function in response to changing environmental conditions. The ER and mitochondria join together at multiple sites and form mitochondria-ER associated membranes that participate in signal transduction pathways that are under active investigation. Our laboratory previously showed that HN protects cells from oxidative stress induced cell death and more recently, described the beneficial role of HN on ER stress-induced apoptosis in retinal pigment epithelium cells and the involvement of ER-mitochondrial cross-talk in cellular protection. The protection was achieved, in part, by the restoration of mitochondrial glutathione that was depleted by ER stress. Thus, HN may be a promising candidate for therapy for diseases that involve both oxidative and ER stress. Developing novel approaches for retinal delivery of HN, its analogues as well as small molecular weight ER stress inhibitors would prove to be a valuable approach in the treatment of age-related macular degeneration.
在本综述中，我们讨论了线粒体与内质网（ER）的相互作用机制，重点关注线粒体衍生肽人胰岛素（HN）在内质网应激中的潜在保护作用。内质网和线粒体是动态细胞器，能够根据环境条件的变化改变其结构和功能。内质网和线粒体在多个位点连接在一起，形成线粒体-内质网相关膜，参与正在积极研究的信号转导途径。我们实验室之前表明，HN可保护细胞免受氧化应激诱导的细胞死亡，最近又描述了HN对视网膜色素上皮细胞内质网应激诱导的细胞凋亡的有益作用，以及内质网-线粒体相互作用在细胞保护中的作用。这种保护部分是通过恢复因内质网应激而耗尽的线粒体谷胱甘肽来实现的。因此，HN可能是治疗涉及氧化应激和内质网应激疾病的有前景的候选药物。开发用于视网膜递送HN、其类似物以及小分子内质网应激抑制剂的新方法，将被证明是治疗年龄相关性黄斑变性的一种有价值的方法。
