刘兴国团队发现线粒体膜间隙的分子伴侣
2021年8月31日, Science China Life Sciences(《中国科学:生命科学》英文版)在线发表了中国科学院广州生物医药与健康研究院刘兴国团队的最新研究成果“Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space”的研究论文,该研究报道了在线粒体这一双膜细胞器中,内外膜之间的膜间隙是来自呼吸链多重损伤的最恶劣胁迫区域,而OPA1的可溶性短链蛋白在这一区域起到分子伴侣(molecular chaperon)帮助蛋白折叠这一全新功能,对于维持线粒体稳态发挥重要作用。
OPA1在多种生理病理中发挥重要作用,刘兴国团队对OPA1在线粒体抗胁迫的作用进行了系统研究,这一持续的工作使人们对于OPA1在线粒体损伤中的“三头六臂”的多重作用有了一个崭新并全面的认识:首先,当线粒体在胁迫条件下时,其膜间隙的可溶性短链蛋白S-OPA1作为分子伴侣,发挥“仁义”的作用,维持线粒体蛋白稳态(Yao et al. 2021);其次,当线粒体通过社交得到外援而功能恢复,OPA1不含外显子4b的剪接体发挥了“情商”的决定作用,可以与其他功能正常的线粒体进行“kiss-and-run”或完全融合得到恢复(Liu et al., 2009);再次,当线粒体自我功能恢复,OPA1含外显子4b的剪接体发挥了“良知”的启动作用,特异结合线粒体DNA的转录的调控区而恢复功能(Yang et al., 2020);最后,当线粒体损伤严重将导致细胞死亡,OPA1则骤然“心碎”释放内嵴的细胞色素c引发凋亡(Li et al., 2015)。
(图二 OPA1在线粒体的多种功能)
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