Caveolin‐1 influences mitochondrial plasticity and function in hepatic stellate cell activation. (16th August 2022)

• Record Type: Journal Article
• Authors: Ilha, Mariana; Meira Martins, Leo A.; da Silveira Moraes, Ketlen; Dias, Camila K.; Thomé, Marcos P.; Petry, Fernanda; Rohden, Francieli; Borojevic, Radovan; Trindade, Vera M. T.; Klamt, Fábio; Barbé‐Tuana, Florência; Lenz, Guido; Guma, Fátima C. R.
• Is Part Of: Cell biology international. Volume 46:Number 11(2022)
• Page Start: 1787
• Page End: 1800
• Publication Date: 2022-08-16
• Subjects: caveolin‐1 -- hepatic stellate cell -- liver fibrosis -- lysosomal activity -- mitochondrial cholesterol -- mitochondrial plasticity; Cytology -- Periodicals; Cells -- Periodicals; 571.605
• DOI: 10.1002/cbin.11876
• Languages: English
• ISSNs: 1065-6995

Abstract

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.