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Ilha 2022 Cell Biol Int

From Bioblast
Publications in the MiPMap
Ilha M, Meira Martins LA, da Silveira Moraes K, Dias CK, Thomé MP, Petry F, Rohden F, Borojevic R, Trindade VMT, Klamt F, Barbé-Tuana F, Lenz G, Guma FCR (2022) Caveolin-1 influences mitochondrial plasticity and function in hepatic stellate cell activation.

» Cell Biol Int [Epub ahead of print]. PMID: 35971753 Open Access

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 (2022) Cell Biol Int

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. Keywords: Caveolin-1, Hepatic stellate cell, Liver fibrosis, Lysosomal activity, Mitochondrial cholesterol, Mitochondrial plasticity Bioblast editor: Plangger M O2k-Network Lab: BR Porto Alegre Klamt F

Labels: MiParea: Respiration, mt-Structure;fission;fusion, Genetic knockout;overexpression 

Organism: Mouse  Tissue;cell: Liver  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k