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  • Scientists Uncovered Intracellular Mechanisms of Cold-induced Apoptosis
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    Most of transmembrane BAX inhibitor motif (TMBIM)-containing family proteins have an anti-apoptotic activity, but their in vivo functions and intracellular mechanisms remain largely unclear.

    Recently, a group led by Prof. CUI Zongbin at Institute of Hydrobiology (IHB) of Chinese Academy of Sciences uncovered the intracellular mechanisms of cold-induced endoplasmic reticulum (ER) stress and apoptosis in zebrafish larvae as well as the functions of Tmbim3a/Grinaa in regulation of ER stress and intracellular Ca2+ homeostasis. Results of this study was published online by Journal of Biological Chemistry. 

    In this study, a mutant zebrafish line was generated, in which the expression of the tmbim3a/grinaa gene was disrupted by a Tol2 transposon insertion. Homozygous tmbim3a/grinaa mutant larvae exhibited an increased mortality and apoptosis under cold exposure at 16°C.  

    Mechanistically, cold exposure triggers suppression of Ca2+-ATPase activity, unfolded protein response and ER stress. The cold-induced ER stress is exaggerated in homozygous tmbim3a/grinaa mutant embryos.  

    Such hyper-sensitivity of tmbim3a/grinaa mutants to cold stress was tightly associated with disrupted intracellular Ca2+ homeostasis, followed by mitochondrial Ca2+ overload and  cytochrome C release, leading to the activation of caspase-9- and caspase-3-mediated intrinsic apoptotic pathway.  

    These findings unveiled a key role of Tmbim3a/Grinaa in cold-induced ER stress and protection against cell death during zebrafish development.This work was mainly supported by the Science Foundation for Creative Research Group of National Natural Science Foundation of China. 

    A working model of cold-induced apoptosis in zebrafish (Image by IHB)


    Prof. CUI Zongbin
    Research Group of Environmental Genomics
    Institute of Hydrobiology, Chinese Academy of Sciences
    E-mail: zbcui@ihb.ac.cn 
  • Deficiency in the membrane protein Tmbim3a/Grinaa initiates cold-induced ER stress and cell death by activating an intrinsic apoptotic pathway in zebrafish
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