Endomembrane specialization allows functional compartmentalization but imposes physical constraints to information flow within the cell. However, the evolution of an endomembrane system was associated with the emergence of contact sites facilitating communication between membrane-bound organelles. Contact sites between the endoplasmic reticulum (ER) and mitochondria are highly conserved in terms of their morphological features but show surprising molecular diversity within and across eukaryote species. ER-mitochondria contact sites are thought to regulate key processes in oncogenesis but their molecular composition remains poorly characterized in mammalian cells. In this study, we investigate the localization of pannexin 2 (Panx2), a membrane channel protein showing tumor-suppressing properties in cancer cells. Using a combination of subcellular fractionation, particle tracking in live-cell, and immunogold electron microscopy, we show that Panx2 localizes at ER-mitochondria contact sites in mammalian cells and sensitizes cells to apoptotic stimuli.
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http://dx.doi.org/10.3390/cancers11030343 | DOI Listing |
Hum Mol Genet
January 2025
Department of Metabolism and Systems Science, University of Birmingham, Birmingham, B15 2TT, United Kingdom.
The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed at hypothalamic neurons that has an important role in appetite suppression and food intake. Mutations in MC4R are the most common cause of monogenic obesity and can affect multiple signaling pathways including Gs-cAMP, Gq, ERK1/2, β-arrestin recruitment, internalization and cell surface expression. The melanocortin-2 receptor accessory protein 2 (MRAP2), is a single-pass transmembrane protein that interacts with and regulates signaling by MC4R.
View Article and Find Full Text PDFObjectives: The goal of this systematic review was to critically appraise the existing evidence evaluating osteoporosis' effects on dental implant osseointegration and survival rate.
Data Source: A search was conducted in two databases, PubMed/MEDLINE and Scopus, until October 2024, using the keywords 'osteoporosis,' 'osteopenia,' 'osseointegration,' and 'dental implants'. The inclusion criteria were clinical studies that evaluated the implant placement, complications, and osseointegration results in patients with osteoporosis; literature reviews and clinical studies addressing the outcome were considered; and articles written in English and published since 2000.
Hepatic lipid accumulation, or Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), is a significant risk factor for liver cancer. Despite the rising incidence of MASLD, the underlying mechanisms of steatosis and lipotoxicity remain poorly understood. Interestingly, lipid accumulation also occurs during fasting, driven by the mobilization of adipose tissue-derived fatty acids into the liver.
View Article and Find Full Text PDFBackground: Bridge-like lipid transfer proteins (BLTPs) mediate bulk lipid transport at membrane contact sites. Mutations in BLTPs are linked to both early-onset neurodevelopmental and later-onset neurodegenerative diseases, including movement disorders. The tissue specificity and temporal requirements of BLTPs in disease pathogenesis remain poorly understood.
View Article and Find Full Text PDFBBA Adv
December 2024
University of São Paulo, Department of Cell and Developmental Biology, Institute of Biomedical Sciences (ICB), São Paulo, 05508-000, Brazil.
Metastases are the leading cause of cancer-related deaths, and their origin is not fully elucidated. Recently, studies have shown that extracellular vesicles (EVs), particularly small extracellular vesicles (sEV), can disrupt the homeostasis of organs, promoting the development of a secondary tumor. However, the role of sEV in brain endothelium and their association with metastasis related to breast cancer is unknown.
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