在这项研究中，课题组人员将细胞合成货物运输试验与AlphaFold2引导的诱变相结合，以鉴定线粒体接头蛋白（运输激酶结合蛋白（TRAK））中的调节螺旋，该螺旋介导激酶驱动和动力蛋白驱动运输之间的转换。螺旋序列的差异解释了为什么两个几乎相同的TRAK同工异构体主要以相反的方向运输线粒体。应激激活激酶对调节螺旋的磷酸化引导了动力蛋白的激活和动力蛋白的解离。他们的研究结果揭示了线粒体在响应细胞内信号时协调定向运输的分子机制。
研究人员表示，线粒体的细胞分布响应于应激和局部能量需求是由基于微管的分子马达的相对活动控制的。在这两个极性相反的微管马达之间切换的机制尚不清楚。
附：英文原文
Title: A molecular switch for coordinating kinesin and dynein transport of mitochondrial cargo
Author: Christina Gladkova, Maria G. Paez-Segala, William P. Grant, Mark Kittisopikul, Samuel A. Myers, Yuxiao Wang, Ronald D. Vale
Issue&Volume: 2026-08-06
Abstract: The cellular distribution of mitochondria in response to stress and local energy needs is governed by the relative activities of the microtubule-based molecular motors kinesin and dynein. The mechanism for switching between these two opposite-polarity microtubule motors remains unknown. In this study, we coupled a cellular synthetic cargo transport assay with AlphaFold2-guided mutagenesis to identify a regulatory helix in the mitochondrial adaptor protein [trafficking kinesin-binding protein (TRAK)] that mediates switching between kinesin- and dynein-driven transport. Differences in the helix sequence explained why two near-identical TRAK isoforms transported mitochondria in predominantly opposite directions. Phosphorylation of the regulatory helix by stress-activated kinases caused the activation of dynein and dissociation of kinesin. Our results reveal a molecular mechanism for coordinating the directional transport of mitochondria in response to intracellular signals.
DOI: aeh1475
Source: https://www.science.org/doi/10.1126/science.aeh1475