Browsing by Author "Cavieres, Viviana A."

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    How Many Sirtuin Genes Are Out There? Evolution of Sirtuin Genes in Vertebrates With a Description of a New Family Member
    (2023) Opazo, Juan Carlos; Vandewege, Michael W.; Hoffmann, Federico G.; Zavala, Kattina; Melendez, Catalina; Luchsinger, Catalina; Cavieres, Viviana A.; Vargas-Chacoff, Luis; Morera, Francisco J.; Burgos Hitschfeld, Patricia Verónica; Tapia-Rojas, Cheril; Mardones, Gonzalo A.
    Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated that it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.
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    KDEL receptor regulates secretion by lysosome relocation- and autophagy-dependent modulation of lipid-droplet turnover
    (2019) Tapia, Diego; Zamora, Constanza; Espinoza, Javier; Rizzo, Riccardo; González Cárdenas, Alexis; Fuentes Peña, Danitza Natalia; Hernández, Sergio; Cavieres, Viviana A.; Guzmán, Fanny; Arriagada, Gloria; Yuseff Sepúlveda, María Isabel; Mardones, Gonzalo A.; Burgos , Patricia V.; Luini, Alberto; González, Alfonso; Cancino, Jorge; Jiménez, Tomás; Soza Gajardo, Andrea
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    Neuronopathic Gaucher disease: Beyond lysosomal dysfunction
    (2022) Arevalo, Nohela B.; Lamaizon, Cristian M.; Cavieres, Viviana A.; Burgos, Patricia V.; alvarez, Alejandra R.; Yanez, Maria J.; Zanlungo, Silvana
    Gaucher disease (GD) is an inherited disorder caused by recessive mutations in the GBA1 gene that encodes the lysosomal enzyme beta-glucocerebrosidase (beta-GC). beta-GC hydrolyzes glucosylceramide (GluCer) into glucose and ceramide in the lysosome, and the loss of its activity leads to GluCer accumulation in different tissues. In severe cases, enzymatic deficiency triggers inflammation, organomegaly, bone disease, and neurodegeneration. Neuronopathic Gaucher disease (nGD) encompasses two different forms of the disease, characterized by chronic or acute damage to the central nervous system (CNS). The cellular and molecular studies that uncover the pathological mechanisms of nGD mainly focus on lysosomal dysfunction since the lysosome is the key organelle affected in GD. However, new studies show alterations in other organelles that contribute to nGD pathology. For instance, abnormal accumulation of GluCer in lysosomes due to the loss of beta-GC activity leads to excessive calcium release from the endoplasmic reticulum (ER), activating the ER-associated degradation pathway and the unfolded protein response. Recent evidence indicates mitophagy is altered in nGD, resulting in the accumulation of dysfunctional mitochondria, a critical factor in disease progression. Additionally, nGD patients present alterations in mitochondrial morphology, membrane potential, ATP production, and increased reactive oxygen species (ROS) levels. Little is known about potential dysfunction in other organelles of the secretory pathway, such as the Golgi apparatus and exosomes. This review focuses on collecting evidence regarding organelle dysfunction beyond lysosomes in nGD. We briefly describe cellular and animal models and signaling pathways relevant to uncovering the pathological mechanisms and new therapeutic targets in GD.
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    Tetrahydrohyperforin (IDN5706) targets the endoplasmic reticulum for autophagy activation : potential mechanism for Alzheimer's disease therapy
    (2016) Gonzáles, Alexis; Cavieres, Viviana A.; Inestrosa Cantín, Nibaldo; Burgos, Patricia V.
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    Tetrahydrohyperforin inhibits the proteolytic processing of amyloid precursor protein and enhances its degradation by Atg5-dependent autophagy
    (2015) Cavieres, Viviana A.; González, Alexis; Muñoz, Vanessa C.; Yefi Rubio, Claudia Pamela; Bustamante, Hianara A.; Barraza, Rafael R.; Tapia Rojas, Cheril Cecilia; Otth, Carola; Barrera, María José; Inestrosa Cantín, Nibaldo; Mardones, Gonzalo A.; González, Carlos; Burgos, Patricia V.