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 research group 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. The study was published in Journal of Biological Chemistry.
In this study, researchers generated a mutant zebrafish line, 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.
They found that 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.
The results unveiled a key role of Tmbim3a/Grinaa in cold-induced ER stress and protection against cell death during zebrafish development.
Intracellular Mechanisms of Cold-induced Apoptosis
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