英属哥伦比亚大学Hilla Weidberg团队宣布他们研究出线粒体靶向序列在信号胁迫中的直接作用。相关论文于2025年12月10日发表于国际顶尖学术期刊《自然》杂志上。

在这里，该课题组研究人员揭示了保守的线粒体Hsp70共同伴侣Mge1在芽殖酵母中充当应激信使。在线粒体应激过程中，未输入的Mge1进入核核，触发mitoCPR靶基因的转录。这是由Mge1与DNA调控元件上的转录因子Pdr3相互作用介导的。Mge1的线粒体靶向序列对于mitoCPR的诱导是充分和必要的，这表明靶向序列除了在线粒体蛋白输入中发挥作用外，还可以作为信号分子发挥作用。由于蛋白质输入缺陷是各种线粒体损伤的常见后果，这些发现表明Mge1靶向序列具有作为线粒体健康指标的新功能。

据了解，线粒体蛋白的输入是维持细胞器功能所必需的。这一过程中的扰动与各种生理和疾病状况有关。几种应激反应，包括线粒体蛋白输入受损反应（mitoCPR），对抗由线粒体蛋白输入缺陷引起的损伤。然而，这种缺陷是如何被感知的，在很大程度上仍然是未知的。

附：英文原文

Title: A direct role for a mitochondrial targeting sequence in signalling stress

Author: Yuan, Zixuan, Balzarini, Megan, Volpe, Marina, Goldstein, Madeleine, Peng, Tony Shengzhe, Hui, Elizabeth, Fang, Nancy Neng, Albihlal, Waleed S., Hajimohammadi, Melika, Wei, Kevin, Yip, Calvin K., van Werven, Folkert J., Mayor, Thibault, Weidberg, Hilla

Issue&Volume: 2025-12-10

Abstract: Mitochondrial protein import is required for maintaining organellar function1. Perturbations in this process are associated with various physiological and disease conditions2. Several stress responses, including the mitochondrial compromised protein import response (mitoCPR), combat damage caused by mitochondrial protein import defects2. However, how this defect is sensed remains largely unknown. Here we reveal that the conserved mitochondrial Hsp70 co-chaperone, Mge1, acts as a stress messenger in budding yeast. During mitochondrial stress, unimported Mge1 entered the nucleus and triggered the transcription of mitoCPR target genes. This was mediated by the interaction of Mge1 with the transcription factor Pdr3 on DNA regulatory elements. The mitochondrial targeting sequence of Mge1 was both sufficient and essential for mitoCPR induction, demonstrating that in addition to their roles in mitochondrial protein import, targeting sequences can also function as signalling molecules. As protein import defects are a common consequence of various types of mitochondrial damage3,4, these findings suggest a novel function for the targeting sequence of Mge1 as an indicator of mitochondrial health.

DOI: 10.1038/s41586-025-09834-x

Source: https://www.nature.com/articles/s41586-025-09834-x