Chen Ying-Chieh, Cheng Tzu-Hao, Lin Wei-Ling, Chen Chang-Lin, Yang Wei Yuan, Blackstone Craig, Chang Chuang-Rung
Institute of Biotechnology, National Tsing Hua University, Life Science Building II, Room 506 No. 101, Section 2, Kuang-Fu Road, Hsin Chu City 30013, Taiwan, ROC.
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei City 11221, Taiwan, ROC.
iScience. 2019 Jan 25;11:305-317. doi: 10.1016/j.isci.2018.12.021. Epub 2018 Dec 26.
Dynamic processes such as fusion, fission, and trafficking are important in the regulation of cellular organelles, with an abundant literature focused on mitochondria. Mitochondrial dynamics not only help shape its network within cells but also are involved in the modulation of respiration and integrity. Disruptions of mitochondrial dynamics are associated with neurodegenerative disorders. Although proteins that directly bind mitochondria to promote membrane fusion/fission have been studied intensively, machineries that regulate dynamic mitochondrial processes remain to be explored. We have identified an interaction between the mitochondrial fission GTPase Dnm1/DRP1 and the actin-regulatory protein Srv2/CAP at mitochondria. Deletion of Srv2 causes elongated-hyperfused mitochondria and reduces the reserved respiration capacity in yeast cells. Our results further demonstrate that the irregular network morphology in Δsrv2 cells derives from disrupted actin assembly at mitochondria. We suggest that Srv2 functions as a pro-fission factor in shaping mitochondrial dynamics and regulating activity through its actin-regulatory effects.
诸如融合、裂变和运输等动态过程在细胞器的调节中很重要，大量文献聚焦于线粒体。线粒体动态变化不仅有助于塑造其在细胞内的网络，还参与呼吸作用和完整性的调节。线粒体动态变化的破坏与神经退行性疾病有关。尽管已经深入研究了直接结合线粒体以促进膜融合/裂变的蛋白质，但调节线粒体动态过程的机制仍有待探索。我们已经确定了线粒体裂变GTP酶Dnm1/DRP1与肌动蛋白调节蛋白Srv2/CAP在线粒体上的相互作用。删除Srv2会导致线粒体拉长 - 过度融合，并降低酵母细胞中的储备呼吸能力。我们的结果进一步证明，Δsrv2细胞中不规则的网络形态源于线粒体处肌动蛋白组装的破坏。我们认为，Srv2作为一种促进裂变的因子，通过其肌动蛋白调节作用来塑造线粒体动态变化并调节其活性。
