Wu Youjun, Ding Chen, Weinreb Alexis, Manning Laura, Swaim Grace, Yogev Shaul, Colón-Ramos Daniel A, Hammarlund Marc
Department of Genetics, Yale University School of Medicine, New Haven, CT 06536, USA.
Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06536, USA.
bioRxiv. 2023 Jul 12:2023.07.12.548706. doi: 10.1101/2023.07.12.548706.
Mitochondria transport is crucial for mitochondria distribution in axons and is mediated by kinesin-1-based anterograde and dynein-based retrograde motor complexes. While Miro and Milton/TRAK were identified as key adaptors between mitochondria and kinesin-1, recent studies suggest the presence of additional mechanisms. In , is the only single gene described so far, other than kinesin-1, that is absolutely required for axonal mitochondria localization. Using CRISPR engineering in , we find that Miro is important but is not essential for anterograde traffic, whereas it is required for retrograde traffic. Both the endogenous RIC-7 and kinesin-1 act at the leading end to transport mitochondria anterogradely. RIC-7 recruitment to mitochondria requires its N-terminal domain and partially relies on MIRO-1, whereas RIC-7 accumulation at the leading end depends on its disordered region, kinesin-1 and metaxin2. We conclude that polarized transport complexes containing kinesin-1 and RIC-7 form at the leading edge of mitochondria, and that these complexes are required for anterograde axonal transport.
线粒体运输对于轴突中线粒体的分布至关重要，并且由基于驱动蛋白-1的顺行和基于动力蛋白的逆行运动复合体介导。虽然米罗（Miro）和米尔顿/ TRAK（Milton/TRAK）被确定为线粒体与驱动蛋白-1之间的关键衔接蛋白，但最近的研究表明还存在其他机制。在[具体生物]中，除了驱动蛋白-1之外，RIC-7是迄今为止描述的唯一对于轴突线粒体定位绝对必需的单个基因。在[具体生物]中使用CRISPR基因编辑技术，我们发现米罗对于顺行运输很重要，但并非必不可少，而逆行运输则需要它。内源性RIC-7和驱动蛋白-1都在前导端起作用，以顺行方式运输线粒体。RIC-7募集到线粒体需要其N末端结构域，并且部分依赖于MIRO-1，而RIC-7在前导端的积累则取决于其无序区域、驱动蛋白-1和变旋蛋白2。我们得出结论，包含驱动蛋白-1和RIC-7的极化运输复合体在线粒体的前缘形成，并且这些复合体是轴突顺行运输所必需的。
