Caveolae: Metabolic Platforms at the Crossroads of Health and Disease

Abstract

Caveolae are small flask-shaped invaginations of the plasma membrane enriched in cholesterol and sphingolipids. They play a critical role in various cellular processes, including signal transduction, endocytosis, and mechanotransduction. Caveolin proteins, specifically Cav-1, Cav-2, and Cav-3, in addition to their role as structural components of caveolae, have been found to regulate the activity of signaling molecules. A growing body of research has highlighted the pivotal role of caveolae and caveolins in maintaining cellular metabolic homeostasis. Indeed, studies have demonstrated that caveolins interact with the key components of insulin signaling, glucose uptake, and lipid metabolism, thereby influencing energy production and storage. The dysfunction of caveolae or the altered expression of caveolins has been associated with metabolic disorders, including obesity, type 2 diabetes, and ocular diseases. Remarkably, mutations in caveolin genes can disrupt cellular energy balance, promote oxidative stress, and exacerbate metabolic dysregulation. This review examines current research on the molecular mechanisms through which caveolae and caveolins regulate cellular metabolism, explores their involvement in the pathogenesis of metabolic disorders, and discusses potential therapeutic strategies targeting caveolin function and the stabilization of caveolae to restore metabolic homeostasis.

Keywords: cardiovascular disease; caveolae; caveolins; endothelial cells; lipid rafts; metabolism; ocular disease.

Figure 1

Model of caveolae and Cav-1 domains. CSD, caveolin scaffolding domain; EHD2, Eps15 homology domain 2; OD, oligomerization domain; S80, phosphorylation at Serine 80; 14, phosphorylation at Tyrosine Y14. (Created with Biorender.com).

Figure 2

Anatomy of the eye (created with Biorender.com).