Caveolin-1 的影响线粒体可塑性和肝星状细胞活化中的功能

Caveolin-1 influences mitochondrial plasticity and function in hepatic stellate cell activation.

Keywords：Caveolin-1, Hepatic stellate cell, Liver fibrosis, Lysosomal activity, Mitochondrial cholesterol, Mitochondrial plasticity

关键词：Caveolin-1、肝星状细胞、肝纤维化、溶酶体活性、线粒体胆固醇、线粒体可塑性

组织：肝脏
作者：Ilha Mariana, Meira Martins Leo A, da Silveira Moraes Ketlen, Dias Camila K, Thome Marcos P, Petry Fernanda, Rohden Francieli, Borojevic Radovan, Trindade Vera MT, Klamt Fabio, Barbe-Tuana Florencia, Lenz Guido, Guma Fatima CR
出版期刊：《Cell BiologyInternational》（2022年）

Abstract：

Caveolin-1 (Cav-1) is an integral membrane protein present in all organelles, responsible for regulating and integrating multiple signals as a platform. Mitochondria are extremely adaptable to external cues in chronic liver diseases, and expression of Cav-1 may affect mitochondrial flexibility in hepatic stellate cells (HSCs) activation. We previously demonstrated that exogenous expression of Cav-1 was sufficient to increase some classical markers of activation in HSCs. Here, we aimed to evaluate the influence of exogenous expression and knockdown of Cav-1 on regulating the mitochondrial plasticity, metabolism, endoplasmic reticulum (ER)-mitochondria distance, and lysosomal activity in HSCs. To characterize the mitochondrial, lysosomal morphology, and ER-mitochondria distance, we perform transmission electron microscope analysis. We accessed mitochondria and lysosomal networks and functions through a confocal microscope and flow cytometry. The expression of mitochondrial machinery fusion/fission genes was examined by real-time polymerase chain reaction. Total and mitochondrial cholesterol content was measured using Amplex Red. To define energy metabolism, we used the Oroboros system in the cells. We report that GRX cells with exogenous expression or knockdown of Cav-1 changed mitochondrial morphometric parameters, OXPHOS metabolism, ER-mitochondria distance, lysosomal activity, and may change the activation state of HSC. This study highlights that Cav-1 may modulate mitochondrial function and structural reorganization in HSC activation, being a potential candidate marker for chronic liver diseases and a molecular target for therapeutic intervention. 

文章摘要：

Caveolin-1 (Cav-1) 是一种完整的膜蛋白，存在于所有细胞器中，负责调节和整合多个信号作为平台。线粒体非常适应慢性肝病的外部线索，Cav-1 的表达可能会影响肝星状细胞 (HSC) 激活中的线粒体灵活性。我们之前证明了 Cav-1 的外源表达足以增加 HSC 中一些经典的激活标志物。在这里，我们旨在评估外源性表达和 Cav-1 敲低对调节 HSC 中线粒体可塑性、代谢、内质网 (ER)-线粒体距离和溶酶体活性的影响。为了表征线粒体、溶酶体形态和 ER-线粒体距离，我们进行了透射电子显微镜分析。我们通过共聚焦显微镜和流式细胞仪访问线粒体和溶酶体网络和功能。通过实时聚合酶链反应检查线粒体机械融合/裂变基因的表达。使用 Amplex Red 测量总胆固醇和线粒体胆固醇含量。为了定义能量代谢，我们在细胞中使用了 Oroboros 系统。我们报告了具有外源性表达或 Cav-1 敲低的 GRX 细胞改变了线粒体形态参数、OXPHOS 代谢、ER-线粒体距离、溶酶体活性，并可能改变 HSC 的激活状态。本研究强调 Cav-1 可能在 HSC 激活过程中调节线粒体功能和结构重组，是慢性肝病的潜在候选标志物和治疗干预的分子靶点。

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