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Malonate induces the assembly of cytoplasmic stress granules
Author(s) -
Fu Xue,
Gao Xingjie,
Ge Lin,
Cui Xiaoteng,
Su Chao,
Yang Wendong,
Sun Xiaoming,
Zhang Wei,
Yao Zhi,
Yang Xi,
Yang Jie
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12049
Subject(s) - malonate , stress granule , mitochondrion , electron transport chain , translation (biology) , cytoplasm , chemistry , phosphorylation , atp synthase , adenosine triphosphate , microbiology and biotechnology , gene knockdown , stimulation , mitochondrial respiratory chain , biophysics , biochemistry , biology , apoptosis , enzyme , messenger rna , endocrinology , gene
Malonate, a classic inhibitor of respiratory electron transport chain, induces mitochondrial stress. Stress granules ( SG s) 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 Δψ m and ATP level. The phosphorylation levels of eIF 2α and 4 EBP 1 protein were affected upon mitochondrial dysfunction. However, knockdown of 4 EBP 1 affected SG formation, rather than eIF 2α. 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 SG s via 4 EBP 1 pathway.