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      Mitochondria-Associated Endoplasmic Reticulum Membranes in Breast Cancer

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          Abstract

          Mitochondria-associated ER membranes (MAMs) represent a crucial intracellular signaling hub, that regulates various cellular events including Ca 2+ homeostasis, lipid metabolism, mitochondrial function, and cellular survival and death. All of these MAM-mediated cellular events contribute to carcinogenesis. Indeed, altered functions of MAMs in several types of cancers have been documented, in particular for breast cancer. Over the past years, altered expression of many MAM-resident proteins have been reported in breast cancer. These MAM-resident proteins play an important role in regulation of breast cancer initiation and progression. In the current review, we discuss our current knowledge about the functions of MAMs, and address the underlying mechanisms through which MAM-resident proteins regulate breast cancer. A fuller understanding of the pathways through which MAMs regulate breast cancer, and identification of breast cancer-specific MAM-resident proteins may help to develop novel therapeutic strategies for breast cancer.

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          Most cited references98

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          Regulation of ferroptotic cancer cell death by GPX4.

          Ferroptosis is a form of nonapoptotic cell death for which key regulators remain unknown. We sought a common mediator for the lethality of 12 ferroptosis-inducing small molecules. We used targeted metabolomic profiling to discover that depletion of glutathione causes inactivation of glutathione peroxidases (GPXs) in response to one class of compounds and a chemoproteomics strategy to discover that GPX4 is directly inhibited by a second class of compounds. GPX4 overexpression and knockdown modulated the lethality of 12 ferroptosis inducers, but not of 11 compounds with other lethal mechanisms. In addition, two representative ferroptosis inducers prevented tumor growth in xenograft mouse tumor models. Sensitivity profiling in 177 cancer cell lines revealed that diffuse large B cell lymphomas and renal cell carcinomas are particularly susceptible to GPX4-regulated ferroptosis. Thus, GPX4 is an essential regulator of ferroptotic cancer cell death. Copyright © 2014 Elsevier Inc. All rights reserved.
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            The NLRP3 inflammasome: molecular activation and regulation to therapeutics

            NLRP3 (NACHT, LRR and PYD domains-containing protein 3) is an intracellular sensor that detects a broad range of microbial motifs, endogenous danger signals and environmental irritants, resulting in the formation and activation of the NLRP3 inflammasome. Assembly of the NLRP3 inflammasome leads to caspase-1-dependent release of the proinflammatory cytokines, IL-1β and IL-18, as well as to gasdermin D-mediated pyroptotic cell death. Recent studies have revealed new regulators of the NLRP3 inflammasome, including new interacting or regulatory proteins, metabolic pathways and a regulatory mitochondrial hub. In this Review, we present the molecular, cell biological and biochemical basis of NLRP3 activation and regulation, and describe how this mechanistic understanding is leading to potential therapeutics that target the NLRP3 inflammasome.
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              Membrane lipids: where they are and how they behave.

              Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?
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                Author and article information

                Contributors
                Journal
                Front Cell Dev Biol
                Front Cell Dev Biol
                Front. Cell Dev. Biol.
                Frontiers in Cell and Developmental Biology
                Frontiers Media S.A.
                2296-634X
                28 January 2021
                2021
                : 9
                : 629669
                Affiliations
                [1] 1Department of Biochemistry and Molecular Biology, Guangzhou Medical University-Guangzhou Institutes of Biomedicine and Health (GMU-GIBH) Joint School of Life Sciences, Guangzhou Medical University , Guangzhou, China
                [2] 2Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University , Guangzhou, China
                Author notes

                Edited by: Simone Patergnani, University of Ferrara, Italy

                Reviewed by: Claudia Giampietri, Sapienza University of Rome, Italy; Soumasree De, University of Bern, Switzerland

                *Correspondence: Qing Gong 443292273@ 123456qq.com

                This article was submitted to Signaling, a section of the journal Frontiers in Cell and Developmental Biology

                †These authors share first authorship

                Article
                10.3389/fcell.2021.629669
                7902067
                33634130
                3a9deba5-ae52-40d6-b486-35e027af9f3c
                Copyright © 2021 Yu, Sun, Gong and Feng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 November 2020
                : 08 January 2021
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 98, Pages: 10, Words: 7688
                Funding
                Funded by: Guangzhou Municipal Science and Technology Project 10.13039/501100010256
                Funded by: Natural Science Foundation of Guangdong Province 10.13039/501100003453
                Categories
                Cell and Developmental Biology
                Review

                mitochodnria,er,mam,breast cancer,carcinogenesis
                mitochodnria, er, mam, breast cancer, carcinogenesis

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