Pfanner Nikolaus, den Brave Fabian, Becker Thomas
Institute of Biochemistry and Molecular Biology, ZBMB, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany.
Nat Cell Biol. 2025 Feb;27(2):188-201. doi: 10.1038/s41556-024-01590-w. Epub 2025 Jan 22.
Mitochondria have to import a large number of precursor proteins from the cytosol. Chaperones keep these proteins in a largely unfolded state and guide them to the mitochondrial import sites. Premature folding, mitochondrial stress and import defects can cause clogging of import sites and accumulation of non-imported precursors, representing a critical burden for cellular proteostasis. Here we discuss how cells respond to mitochondrial protein import stress by regenerating clogged import sites and inducing stress responses. The mitochondrial protein import machinery has a dual role by serving as sensor for detecting mitochondrial dysfunction and inducing stress-response pathways. The production of chaperones that fold or sequester precursor proteins in deposits is induced and the proteasomal activity is increased to remove the excess precursor proteins. Together, these pathways reveal how mitochondria are tightly integrated into a cellular proteostasis and stress response network to maintain cell viability.
线粒体必须从细胞质中导入大量前体蛋白。分子伴侣使这些蛋白大多保持未折叠状态，并将它们引导至线粒体导入位点。过早折叠、线粒体应激和导入缺陷会导致导入位点堵塞以及未导入前体的积累，这对细胞蛋白质稳态构成了关键负担。在此，我们讨论细胞如何通过再生堵塞的导入位点和诱导应激反应来应对线粒体蛋白导入应激。线粒体蛋白导入机制具有双重作用，它可作为检测线粒体功能障碍的传感器并诱导应激反应途径。诱导产生能使前体蛋白折叠或隔离在前体沉积物中的分子伴侣，并提高蛋白酶体活性以去除多余的前体蛋白。总之，这些途径揭示了线粒体是如何紧密地整合到细胞蛋白质稳态和应激反应网络中以维持细胞活力的。
