title: Malonate induces the assembly of cytoplasmic stress granules.
abstract: Malonate, a classic inhibitor of respiratory electron transport chain, induces mitochondrial stress. Stress granules (SGs) are a kind of dynamic foci structure during stress. The study on the connection of mitochondrial stress and SG assembly is still limited. Here, we demonstrated that malonate treatment leads to SG formation and translation inhibition, apart from mitochondrial stress, including enhanced ROS formation, reduced mitochondrial Δψm and ATP level. The phosphorylation levels of eIF2α and 4EBP1 protein were affected upon mitochondrial dysfunction. However, knockdown of 4EBP1 affected SG formation, rather than eIF2α. In addition, an increase of ATP level under mitochondrial stress enhanced malonate-induced SG aggregation. Overall, malonate stimulation triggers mitochondrial stress and induces the assembly of non-canonical cellular SGs via 4EBP1 pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Xingjie
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Xiaoteng
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Su
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, China.|Laboratory of Molecular Immunology, Research Center of Basic Medical Science, Tianjin Medical University, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin Medical University, China.|Key Laboratory of Educational Ministry of China, Tianjin Medical University, China.|Department of Immunology, University of Manitoba, Winnipeg, Canada.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000819:agonists / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D018797:Cell Cycle Proteins; D049109:Cell Proliferation / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects*; D042963:Electron Transport Complex II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008314:Malonates / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001678:Organelle Biogenesis; D018384:Oxidative Stress / Q000187:drug effects*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D008314:Malonates; D010750:Phosphoproteins; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C030290:malonic acid; D042963:Electron Transport Complex II
keywords: 4E binding protein 1; adenosine triphosphate; eukaryotic initiation factor 2 alpha; malonate; mitochondria; phosphorylation; stress granules