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

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.

Long-term administration of Western diet induced metabolic syndrome in mice and causes cardiac microvascular dysfunction, cardiomyocyte mitochondrial damage, and cardiac remodeling involving caveolae and caveolin-1 expression

“…Relevant studies have confirmed that CAV-1 plays an integral role in maintaining mitochondrial shape, plasticity, and function, and loss of CAV-1 promotes mitochondrial senescence and dysfunction [ 42 – 44 ]. Related studies have indicated that CAV-1 in the ER regulates lipid metabolism, ER stress, and maintenance of MAM function.…”

Metabolic Deregulation in Pulmonary Hypertension

“…We have added the analyses on Cav1 because this protein was recently reported to play important roles in the glucose metabolic network [ 52 ], lipid metabolism [ 53 ], mitochondrial metabolism [ 54 ], and in cellular metabolic reprogramming [ 55 ]. There is also experimental evidence regarding the role of Ngf in cellular energy homeostasis [ 56 ].…”

A Review of the Role of Caveolin-1 in Acetaminophen-Induced Liver Injury

“…In normal liver tissue, the morphological feature of hepatic stellate cells is the presence of multiple cytoplasmic lipid droplets (LDs). The cave is a small spherical invagination of the plasma membrane, playing an important role in endocytosis, cell transformation, maintaining membrane lipid composition, and signal transduction [52]. CAV-1 is related to the formation of LDs in human hepatic stellate cells, mainly by lateral fissure or cave endocytosis, which transports newly synthesized cholesterol from the endoplasmic reticulum membrane to the plasma membrane vesicles, where it is transported to high-density lipoprotein in the plasma membrane.…”