Examinando por Autor "Parra, Valentina"
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Ítem Estrogen signaling as a bridge between the nucleus and mitochondria in cardiovascular diseases(Frontiers Media S.A., 2022-09) Guajardo-Correa, Emanuel; Silva-Agüero, Juan Francisco; Calle, Ximena; Chiong, Mario; Henríquez, Mauricio; García-Rivas, Gerardo; Latorre, Mauricio; Parra, ValentinaCardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Epidemiological studies indicate that pre-menopausal women are more protected against the development of CVDs compared to men of the same age. This effect is attributed to the action/effects of sex steroid hormones on the cardiovascular system. In this context, estrogen modulates cardiovascular function in physiological and pathological conditions, being one of the main physiological cardioprotective agents. Here we describe the common pathways and mechanisms by which estrogens modulate the retrograde and anterograde communication between the nucleus and mitochondria, highlighting the role of genomic and non-genomic pathways mediated by estrogen receptors. Additionally, we discuss the presumable role of bromodomain-containing protein 4 (BRD4) in enhancing mitochondrial biogenesis and function in different CVD models and how this protein could act as a master regulator of estrogen protective activity. Altogether, this review focuses on estrogenic control in gene expression and molecular pathways, how this activity governs nucleus-mitochondria communication, and its projection for a future generation of strategies in CVDs treatment.Ítem Myristate induces mitochondrial fragmentation and cardiomyocyte hypertrophy through mitochondrial E3 ubiquitin ligase MUL1(Frontiers Media S.A., 2023-03) Vásquez-Trincado, César; Navarro-Márquez, Mario; Morales, Pablo E.; Westermeier, Francisco; Chiong, Mario; Parra, Valentina; Espinosa, Alejandra; Lavandero, SergioIntroduction: Cardiovascular diseases, especially metabolic-related disorders, are progressively growing worldwide due to high-fat-containing foods, which promote a deleterious response at the cellular level, termed lipotoxicity, or lipotoxic stress. At the cardiac level, saturated fatty acids have been directly associated with cardiomyocyte lipotoxicity through various pathological mechanisms involving mitochondrial dysfunction, oxidative stress, and ceramide production, among others. However, integrative regulators connecting saturated fatty acid-derived lipotoxic stress to mitochondrial and cardiomyocyte dysfunction remain elusive. Methods: Here, we worked with a cardiomyocyte lipotoxicity model, which uses the saturated fatty acid myristate, which promotes cardiomyocyte hypertrophy and insulin desensitization. Results: Using this model, we detected an increase in the mitochondrial E3 ubiquitin ligase, MUL1, a mitochondrial protein involved in the regulation of growth factor signaling, cell death, and, notably, mitochondrial dynamics. In this context, myristate increased MUL1 levels and induced mitochondrial fragmentation, associated with the decrease of the mitochondrial fusion protein MFN2, and with the increase of the mitochondrial fission protein DRP1, two targets of MUL1. Silencing of MUL1 prevented myristate-induced mitochondrial fragmentation and cardiomyocyte hypertrophy. Discussion: These data establish a novel connection between cardiomyocytes and lipotoxic stress, characterized by hypertrophy and fragmentation of the mitochondrial network, and an increase of the mitochondrial E3 ubiquitin ligase MUL1. Copyright © 2023 Vásquez-Trincado, Navarro-Márquez, Morales, Westermeier, Chiong, Parra, Espinosa and Lavandero.