| Caveolin-1 Deficiency Causes Cholesterol-Dependent Mitochondrial Dysfunction and Apoptotic Susceptibility. | |
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MedLine Citation:
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PMID: 21497090 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Caveolins (CAVs) are essential components of caveolae, plasma membrane invaginations with reduced fluidity, reflecting cholesterol accumulation [1]. CAV proteins bind cholesterol, and CAV's ability to move between cellular compartments helps control intracellular cholesterol fluxes [1-3]. In humans, CAV1 mutations result in lipodystrophy, cell transformation, and cancer [4-7]. CAV1 gene-disrupted mice exhibit cardiovascular diseases, diabetes, cancer, atherosclerosis, and pulmonary fibrosis [8, 9]. The mechanism or mechanisms underlying these disparate effects are unknown, but our past work suggested that CAV1 deficiency might alter metabolism: CAV1(-/-) mice exhibit impaired liver regeneration unless supplemented with glucose, suggesting systemic inefficiencies requiring additional metabolic intermediates [10]. Establishing a functional link between CAV1 and metabolism would provide a unifying theme to explain these myriad pathologies [11]. Here we demonstrate that impaired proliferation and low survival with glucose restriction is a shortcoming of CAV1-deficient cells caused by impaired mitochondrial function. Without CAV1, free cholesterol accumulates in mitochondrial membranes, increasing membrane condensation and reducing efficiency of the respiratory chain and intrinsic antioxidant defense. Upon activation of oxidative phosphorylation, this promotes accumulation of reactive oxygen species, resulting in cell death. We confirm that this mitochondrial dysfunction predisposes CAV1-deficient animals to mitochondrial-related diseases such as steatohepatitis and neurodegeneration. |
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Authors:
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Marta Bosch; Montserrat Marí; Albert Herms; Ana Fernández; Alba Fajardo; Adam Kassan; Albert Giralt; Anna Colell; David Balgoma; Elisabet Barbero; Elena González-Moreno; Nuria Matias; Francesc Tebar; Jesús Balsinde; Marta Camps; Carlos Enrich; Steven P Gross; Carmen García-Ruiz; Esther Pérez-Navarro; José C Fernández-Checa; Albert Pol |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-14 |
Journal Detail:
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Title: Current biology : CB Volume: - ISSN: 1879-0445 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107782 Medline TA: Curr Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Equip de Proliferació i Senyalització Cel·lular, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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