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Redox Biology Jun 2022As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular...
As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular homeostasis. Here we show that knockdown of the membrane-inserted scaffolding and structural protein caveolin-1 (Cav-1) and expression of tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered mitochondrial morphology, and increased mitochondrial matrix mixing, mitochondrial fusion and fission dynamics as well as mitophagy in MDA-MB-231 triple negative breast cancer cells. Further, we found that interaction of Cav-1 with mitochondrial fusion/fission machinery Mitofusin 2 (Mfn2) and Dynamin related protein 1 (Drp1) was enhanced by Y14D mutant indicating Cav-1 Y14 phosphorylation prevented Mfn2 and Drp1 translocation to mitochondria. Moreover, limiting mitochondrial recruitment of Mfn2 diminished formation of the PINK1/Mfn2/Parkin complex required for initiation of mitophagy resulting in accumulation of damaged mitochondria and ROS (mtROS). Thus, these studies indicate that phospho-Cav-1 may be an important switch mechanism in cancer cell survival which could lead to novel strategies for complementing cancer therapies.
Topics: Caveolin 1; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins; Mitophagy; Reactive Oxygen Species
PubMed: 35413643
DOI: 10.1016/j.redox.2022.102304 -
Molecular Cancer Nov 2016Caveolin-1 (CAV1) is an oncogenic membrane protein associated with endocytosis, extracellular matrix organisation, cholesterol distribution, cell migration and... (Review)
Review
Caveolin-1 (CAV1) is an oncogenic membrane protein associated with endocytosis, extracellular matrix organisation, cholesterol distribution, cell migration and signaling. Recent studies reveal that CAV1 is involved in metabolic alterations - a critical strategy adopted by cancer cells to their survival advantage. Consequently, research findings suggest that CAV1, which is altered in several cancer types, influences tumour development or progression by controlling metabolism. Understanding the molecular interplay between CAV1 and metabolism could help uncover druggable metabolic targets or pathways of clinical relevance in cancer therapy. Here we review from a cancer perspective, the findings that CAV1 modulates cell metabolism with a focus on glycolysis, mitochondrial bioenergetics, glutaminolysis, fatty acid metabolism, and autophagy.
Topics: Animals; Autophagy; Caveolin 1; Energy Metabolism; Fatty Acids; Gene Expression Regulation, Neoplastic; Glutamine; Glycolysis; Humans; Insulin Resistance; Metabolic Networks and Pathways; Mitochondria; Neoplasms; Obesity
PubMed: 27852311
DOI: 10.1186/s12943-016-0558-7 -
Cell Oct 2018We have uncovered the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue (AT) proper. This phenomenon became evident...
We have uncovered the existence of extracellular vesicle (EV)-mediated signaling between cell types within the adipose tissue (AT) proper. This phenomenon became evident in our attempts at generating an adipocyte-specific knockout of caveolin 1 (cav1) protein. Although we effectively ablated the CAV1 gene in adipocytes, cav1 protein remained abundant. With the use of newly generated mouse models, we show that neighboring endothelial cells (ECs) transfer cav1-containing EVs to adipocytes in vivo, which reciprocate by releasing EVs to ECs. AT-derived EVs contain proteins and lipids capable of modulating cellular signaling pathways. Furthermore, this mechanism facilitates transfer of plasma constituents from ECs to the adipocyte. The transfer event is physiologically regulated by fasting/refeeding and obesity, suggesting EVs participate in the tissue response to changes in the systemic nutrient state. This work offers new insights into the complex signaling mechanisms that exist among adipocytes, stromal vascular cells, and, potentially, distal organs.
Topics: Adipocytes; Animals; Caveolin 1; Cell Line; Cells, Cultured; Endothelial Cells; Endothelium, Vascular; Extracellular Vesicles; Fasting; Male; Mice; Mice, Inbred C57BL; Signal Transduction
PubMed: 30293865
DOI: 10.1016/j.cell.2018.09.005 -
Frontiers in Immunology 2024
Topics: Humans; Caveolins; Caveolin 1; Membrane Proteins; Inflammation
PubMed: 38504989
DOI: 10.3389/fimmu.2024.1387191 -
ELife Jun 2023Ring-like structures made up of caveolae appear to drive the development of membrane invaginations called T-tubules which are important for muscle contraction.
Ring-like structures made up of caveolae appear to drive the development of membrane invaginations called T-tubules which are important for muscle contraction.
Topics: Caveolin 1; Caveolae; Endocytosis
PubMed: 37339063
DOI: 10.7554/eLife.88954 -
Progress in Retinal and Eye Research Nov 2022Caveolae, specialized plasma membrane invaginations present in most cell types, play important roles in multiple cellular processes including cell signaling, lipid... (Review)
Review
Caveolae, specialized plasma membrane invaginations present in most cell types, play important roles in multiple cellular processes including cell signaling, lipid uptake and metabolism, endocytosis and mechanotransduction. They are found in almost all cell types but most abundant in endothelial cells, adipocytes and fibroblasts. Caveolin-1 (Cav1), the signature structural protein of caveolae was the first protein associated with caveolae, and in association with Cavin1/PTRF is required for caveolae formation. Genetic ablation of either Cav1 or Cavin1/PTRF downregulates expression of the other resulting in loss of caveolae. Studies using Cav1-deficient mouse models have implicated caveolae with human diseases such as cardiomyopathies, lipodystrophies, diabetes and muscular dystrophies. While caveolins and caveolae are extensively studied in extra-ocular settings, their contributions to ocular function and disease pathogenesis are just beginning to be appreciated. Several putative caveolin/caveolae functions are relevant to the eye and Cav1 is highly expressed in retinal vascular and choroidal endothelium, Müller glia, the retinal pigment epithelium (RPE), and the Schlemm's canal endothelium and trabecular meshwork cells. Variants at the CAV1/2 gene locus are associated with risk of primary open angle glaucoma and the high risk HTRA1 variant for age-related macular degeneration is thought to exert its effect through regulation of Cav1 expression. Caveolins also play important roles in modulating retinal neuroinflammation and blood retinal barrier permeability. In this article, we describe the current state of caveolin/caveolae research in the context of ocular function and pathophysiology. Finally, we discuss new evidence showing that retinal Cav1 exists and functions outside caveolae.
Topics: Mice; Animals; Humans; Caveolae; Caveolin 1; Mechanotransduction, Cellular; Endothelial Cells; Glaucoma, Open-Angle; Homeostasis; High-Temperature Requirement A Serine Peptidase 1
PubMed: 35729002
DOI: 10.1016/j.preteyeres.2022.101094 -
Frontiers in Immunology 2022The skin is the outermost layer and largest organ in the human body. Since the skin interfaces with the environment, it has a variety of roles, including providing a... (Review)
Review
The skin is the outermost layer and largest organ in the human body. Since the skin interfaces with the environment, it has a variety of roles, including providing a protective barrier against external factors, regulating body temperature, and retaining water in the body. It is also involved in the immune system, interacting with immune cells residing in the dermis. Caveolin-1 (CAV-1) is essential for caveolae formation and has multiple functions including endocytosis, lipid homeostasis, and signal transduction. CAV-1 is known to interact with a variety of signaling molecules and receptors and may influence cell proliferation and migration. Several skin-related disorders, especially those of the inflammatory or hyperproliferative type such as skin cancers, psoriasis, fibrosis, and wound healing, are reported to be associated with aberrant CAV-1 expression. In this review, we have explored CAV-1 involvement in skin physiology and skin diseases.
Topics: Humans; Caveolin 1; Skin Diseases; Skin; Signal Transduction; Psoriasis
PubMed: 36532050
DOI: 10.3389/fimmu.2022.1035451 -
The Journal of Cell Biology May 2003Although caveolae are well-characterized subdomains of glycolipid rafts, their distinctive morphology and association with caveolins has led to their internalization... (Review)
Review
Although caveolae are well-characterized subdomains of glycolipid rafts, their distinctive morphology and association with caveolins has led to their internalization being considered different from that of rafts. In this review, we propose that caveolae and rafts are internalized via a common pathway, caveolae/raft-dependent endocytosis, defined by its clathrin independence, dynamin dependence, and sensitivity to cholesterol depletion. The regulatory role of caveolin-1 and ligand sorting in this complex endocytic pathway are specifically addressed.
Topics: Animals; Caveolae; Caveolin 1; Caveolins; Cholesterol; Cytoplasmic Vesicles; Endocytosis; Membrane Microdomains
PubMed: 12771123
DOI: 10.1083/jcb.200302028 -
International Journal of Cancer Oct 2020Metabolic phenotypes of cancer cells are heterogeneous and flexible as a tumor mass is a hurriedly evolving system capable of constant adaptation to oxygen and nutrient... (Review)
Review
Metabolic phenotypes of cancer cells are heterogeneous and flexible as a tumor mass is a hurriedly evolving system capable of constant adaptation to oxygen and nutrient availability. The exact type of cancer metabolism arises from the combined effects of factors intrinsic to the cancer cells and factors proposed by the tumor microenvironment. As a result, a condition termed oncogenic metabolic symbiosis in which components of the tumor microenvironment (TME) promote tumor growth often occurs. Understanding how oncogenic metabolic symbiosis emerges and evolves is crucial for perceiving tumorigenesis. The process by which tumor cells reprogram their TME involves many mechanisms, including changes in intercellular communication, alterations in metabolic phenotypes of TME cells, and rearrangement of the extracellular matrix. It is possible that one molecule with a pleiotropic effect such as Caveolin-1 may affect many of these pathways. Here, we discuss the significance of Caveolin-1 in establishing metabolic symbiosis in TME.
Topics: Caveolin 1; Cell Communication; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; Symbiosis; Tumor Microenvironment
PubMed: 32196654
DOI: 10.1002/ijc.32987 -
Physiological Reviews Oct 2004Although they were discovered more than 50 years ago, caveolae have remained enigmatic plasmalemmal organelles. With their characteristic "flasklike" shape and virtually... (Review)
Review
Although they were discovered more than 50 years ago, caveolae have remained enigmatic plasmalemmal organelles. With their characteristic "flasklike" shape and virtually ubiquitous tissue distribution, these interesting structures have been implicated in a wide range of cellular functions. Similar to clathrin-coated pits, caveolae function as macromolecular vesicular transporters, while their unique lipid composition classifies them as plasma membrane lipid rafts, structures enriched in a variety of signaling molecules. The caveolin proteins (caveolin-1, -2, and -3) serve as the structural components of caveolae, while also functioning as scaffolding proteins, capable of recruiting numerous signaling molecules to caveolae, as well as regulating their activity. That so many signaling molecules and signaling cascades are regulated by an interaction with the caveolins provides a paradigm by which numerous disease processes may be affected by ablation or mutation of these proteins. Indeed, studies in caveolin-deficient mice have implicated these structures in a host of human diseases, including diabetes, cancer, cardiovascular disease, atherosclerosis, pulmonary fibrosis, and a variety of degenerative muscular dystrophies. In this review, we provide an in depth summary regarding the mechanisms by which caveolae and caveolins participate in human disease processes.
Topics: Amino Acid Sequence; Animals; Caveolae; Caveolin 1; Caveolins; Disease; Humans; Molecular Sequence Data; Sequence Homology; Signal Transduction
PubMed: 15383654
DOI: 10.1152/physrev.00046.2003