Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Motooka 744, Nishi-ku, Fukuoka 819-0395, Japan.
J Biochem. 2023 Jun 30;174(1):13-20. doi: 10.1093/jb/mvad025.
Protein targeting to organelles has been thought to be a very precise process, and proteins that fail to localize correctly are rapidly degraded. Tail-anchored proteins are posttranslationally targeted to the endoplasmic reticulum membrane via guided entry of tail-anchored (TA) proteins pathway. However, these proteins can be mislocalized to the mitochondrial outer membrane. We found that the AAA-ATPase Msp1 on the mitochondrial outer membrane extracts mislocalized TA proteins to the cytosol, passing them to the guided entry of the TA proteins pathway to facilitate their transfer to the endoplasmic reticulum membrane. After the transfer to the endoplasmic reticulum, such TA proteins are directed to degradation if they are recognized by the quality control system on the endoplasmic reticulum. If not recognized, they are retargeted to their original destination along the secretory pathway. Thus, we have identified an intracellular proofreading system that corrects the localization of TA proteins.
蛋白质靶向细胞器被认为是一个非常精确的过程，而那些不能正确定位的蛋白质会迅速降解。尾部锚定蛋白通过尾部锚定（TA）蛋白途径的引导进入内质网膜进行翻译后靶向定位。然而，这些蛋白质可能会错误定位到线粒体的外膜。我们发现，线粒体外膜上的 AAA-ATPase Msp1 将错误定位的 TA 蛋白提取到细胞质中，将其传递到 TA 蛋白途径的引导进入，以促进它们转移到内质网膜。转移到内质网后，如果这些 TA 蛋白被内质网的质量控制系统识别，它们就会被定向降解。如果没有被识别，它们就会沿着分泌途径重新靶向到它们的原始目的地。因此，我们已经确定了一个细胞内的校对系统，可以纠正 TA 蛋白的定位。
