mitoCPR - a surveillance pathway that protects mitochondria in response to mitochondrial import stress [yeast]

Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Physiological perturbations and disease conditions can lead to mitochondrial import defect. We find that in budding yeast, mitochondrial import defects result in activation of a surveillance mechanism, which we termed mitoCPR. The mitoCPR is aimed at ameliorating mitochondrial import and protecting mitochondria during import stress. This is mediated by the mitoCPR effector, Cis1, which associates with mitochondria to reduce the accumulation of mitochondrial preproteins at the organelle's surface. Clearance of preproteins depends on the AAA-ATPase Msp1 and the proteasome, suggesting that Cis1 facilitates the degradation of unimported proteins that accumulate at the mitochondrial surface. We further show that mitoCPR is critical for maintaining mitochondrial functions during mitochondrial import stress and provide evidence that it is an ancient, conserved mitochondrial protection mechanism. Overall design: Two replicates each of WT controls, Psd1_oe2 samples (overexpressing Psd1) and Psd1_oe_Pdr3_ko2 samples (overexpressing Psd1 with a Pdr3 deletion) were compared.线粒体功能对于细胞存活至关重要，且依赖于蛋白质向该细胞器的导入过程。生理扰动与疾病状态均可引发线粒体导入缺陷。我们在酿酒酵母中发现，线粒体导入缺陷会激活一种监测机制，我们将其命名为mitoCPR。mitoCPR的作用是改善线粒体导入过程，并在导入应激状态下保护线粒体。该过程由mitoCPR效应因子Cis1介导，Cis1可与线粒体结合，以减少线粒体前体蛋白在细胞器表面的积累。前体蛋白的清除依赖于AAA-ATP酶（AAA-ATPase）Msp1与蛋白酶体，这表明Cis1可促进积累在线粒体外表面的未导入蛋白的降解。我们进一步证实，mitoCPR在线粒体导入应激状态下对维持线粒体功能至关重要，并提供证据表明其是一种古老且保守的线粒体保护机制。实验设计：分别对野生型（WT）对照样本、Psd1过表达样本（Psd1_oe2，即过表达Psd1）以及Psd1过表达且Pdr3敲除样本（Psd1_oe_Pdr3_ko2，即过表达Psd1并缺失Pdr3）各设置两个生物学重复进行比较。