Mitochondrial ROS in Slc4a11 KO Corneal Endothelial Cells Lead to ER Stress.
Mitochondrial ROS in Slc4a11 KO Corneal Endothelial Cells Lead to ER Stress.
复制标题
Slc4a11 KO角膜内皮细胞中线粒体ROS导致ER应激
DOI：
10.3389/fcell.2022.878395
复制
发表时间：
2022
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
最近来自SLC4a11−/−小鼠的研究发现，在这种先天性遗传性内皮营养不良(CHED)模型中，谷氨酰胺诱导的线粒体功能障碍是导致氧化应激、溶酶体功能受损、异常自噬和细胞死亡的重要因素。由于溶酶体来源于内质网(ER)-高尔基体，我们询问SLC4a11 KO角膜内皮细胞的线粒体ROS是否影响ER的功能。在小鼠SLC4a11−/−角膜内皮组织中，我们观察到内质网扩张和ER应激标记物BIP和CHOP的表达增加。与WT相比，与谷氨酰胺孵育的SLC4a11 KO小鼠角膜内皮细胞表现出更多的侵袭体形成、BIP和GADD153，以及减少内质网钙释放。ETC抑制诱导的mitoROS也导致WT细胞内质网应激。线粒体ROS猝灭剂MitoQ可恢复SLC4a11 KO细胞内质网钙离子释放，减轻内质网应激标志物。系统的MitoQ也降低了SLC4a11 KO内皮细胞BIP的表达。结论：线粒体ROS可诱导角膜内皮细胞发生内质网应激。
Recent studies from Slc4a11 −/− mice have identified glutamine-induced mitochondrial dysfunction as a significant contributor toward oxidative stress, impaired lysosomal function, aberrant autophagy, and cell death in this Congenital Hereditary Endothelial Dystrophy (CHED) model. Because lysosomes are derived from endoplasmic reticulum (ER)—Golgi, we asked whether ER function is affected by mitochondrial ROS in Slc4a11 KO corneal endothelial cells. In mouse Slc4a11 −/− corneal endothelial tissue, we observed the presence of dilated ER and elevated expression of ER stress markers BIP and CHOP. Slc4a11 KO mouse corneal endothelial cells incubated with glutamine showed increased aggresome formation, BIP and GADD153, as well as reduced ER Ca2+ release as compared to WT. Induction of mitoROS by ETC inhibition also led to ER stress in WT cells. Treatment with the mitochondrial ROS quencher MitoQ, restored ER Ca2+ release and relieved ER stress markers in Slc4a11 KO cells in vitro. Systemic MitoQ also reduced BIP expression in Slc4a11 KO endothelium. We conclude that mitochondrial ROS can induce ER stress in corneal endothelial cells.
登录
查看更多内容
影响因子：
4.4
作者：
Ogando DG;Shyam R;Kim ET;Wang YC;Liu CY;Bonanno JA
通讯作者：
Bonanno JA
影响因子：
17.8
作者：
Ong Tone S;Kocaba V;Böhm M;Wylegala A;White TL;Jurkunas UV
通讯作者：
Jurkunas UV
影响因子：
13.8
作者：
Senft, Daniela;Ronai, Ze'ev A.
通讯作者：
Ronai, Ze'ev A.
帕金森病中内质网应激、自噬和神经变性的交联
影响因子：
4.8
作者：
Ren H;Zhai W;Lu X;Wang G
通讯作者：
Wang G
影响因子：
4.6
作者：
Guha S;Chaurasia S;Ramachandran C;Roy S
通讯作者：
Roy S