A direct role for a mitochondrial targeting sequence in triggering a stress response

Mitochondrial protein import is required for maintaining organellar function. Perturbations in this process are associated with various physiological and disease conditions. Several stress responses, including the mitoCPR, combat damage caused by mitochondrial protein import stress. However, it remains unknown how this defect is sensed. 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 Mge1’s interaction with the transcription factor Pdr3 on DNA regulatory elements. Mge1’s mitochondrial targeting sequence 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 signaling molecules.线粒体蛋白导入对于维持细胞器功能必不可少。该过程的功能紊乱与多种生理状态及疾病密切相关。包括mitoCPR在内的多种应激应答机制，可抵御线粒体蛋白导入应激所造成的损伤。然而，目前学界尚未明确该应激缺陷的感知机制。本研究揭示，在酿酒酵母中，保守的线粒体热休克蛋白70（Hsp70）共伴侣蛋白Mge1可作为应激信使发挥作用。当线粒体应激发生时，未完成导入的Mge1会转位进入细胞核，并触发mitoCPR靶基因的转录。该过程由Mge1与DNA调控元件上的转录因子Pdr3的相互作用所介导。Mge1的线粒体靶向序列对于mitoCPR的诱导既是充分条件也是必要条件，这表明靶向序列除参与线粒体蛋白导入过程外，还可作为信号分子行使功能。