Mitochondria-associated myosin 19 processively transports mitochondria on actin tracks in living cells.
Mitochondria-associated myosin 19 processively transports mitochondria on actin tracks in living cells.
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DOI：
10.1016/j.jbc.2022.101883
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发表时间：
2022-05
影响因子：
4.8
通讯作者：
Ikebe, Mitsuo
中科院分区：
文献类型：
--
作者：
Sato, Osamu;Sakai, Tsuyoshi;Choo, Young-yeon;Ikebe, Reiko;Watanabe, Tomonobu M.;Ikebe, Mitsuo
线粒体在细胞功能中起着至关重要的作用，它们的功能失调会导致癌症、心血管疾病和神经疾病的发展。肌球蛋白19 （Myo19）显示出线粒体的离散定位，并被认为在线粒体动力学和功能中起重要作用；然而，在细胞和分子水平上，Myo19在线粒体动力学中的功能尚不清楚。关键的缺失信息是Myo19是否是一个适合线粒体运输的过程马达。在这里，我们首次发现单个Myo19分子在肌动蛋白丝上连续移动，并能在细胞中运输线粒体。研究人员发现，在去膜细胞中，具有亮氨酸拉链的Myo19二聚体在细胞肌动蛋白轨道上以50 ~ 60 nm/s的速度和0.4 μm的长度在肌动蛋白轨道上移动，这与Myo19二聚体转染细胞中分离的线粒体在肌动蛋白轨道上的移动相似，表明Myo19二聚体可以运输线粒体。此外，我们显示Myo19二聚体的单分子在单个肌动蛋白丝上以大步长约34 nm的速度行进。重要的是，没有亮氨酸拉链的WT Myo19单分子在活细胞中与Myo19二聚体类似，在丝状伪足中持续移动，而尾部结构域的缺失则会取消这种活跃的运动。这些结果表明，当两个Myo19单体形成二聚体时，Myo19可以在肌动蛋白丝上向前移动，这可能是尾尾结合的结果。综上所述，Myo19分子可以在活细胞内通过肌动蛋白轨道直接运输线粒体。
Mitochondria are fundamentally important in cell function, and their malfunction can cause the development of cancer, cardiovascular disease, and neuronal disorders. Myosin 19 (Myo19) shows discrete localization with mitochondria and is thought to play an important role in mitochondrial dynamics and function; however, the function of Myo19 in mitochondrial dynamics at the cellular and molecular levels is poorly understood. Critical missing information is whether Myo19 is a processive motor that is suitable for transportation of mitochondria. Here, we show for the first time that single Myo19 molecules processively move on actin filaments and can transport mitochondria in cells. We demonstrate that Myo19 dimers having a leucine zipper processively moved on cellular actin tracks in demembraned cells with a velocity of 50 to 60 nm/s and a run length of ∼0.4 μm, similar to the movement of isolated mitochondria from Myo19 dimer-transfected cells on actin tracks, suggesting that the Myo19 dimer can transport mitochondria. Furthermore, we show single molecules of Myo19 dimers processively moved on single actin filaments with a large step size of ∼34 nm. Importantly, WT Myo19 single molecules without the leucine zipper processively move in filopodia in living cells similar to Myo19 dimers, whereas deletion of the tail domain abolished such active movement. These results suggest that Myo19 can processively move on actin filaments when two Myo19 monomers form a dimer, presumably as a result of tail–tail association. In conclusion, Myo19 molecules can directly transport mitochondria on actin tracks within living cells.
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影响因子：
2.9
作者：
Adikes, Rebecca C.;Unrath, William C.;Yengo, Christopher M.;Quintero, Omar A.
通讯作者：
Quintero, Omar A.
DOI：
10.1083/jcb.200601067
发表时间：
2006-05-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glater EE;Megeath LJ;Stowers RS;Schwarz TL
通讯作者：
Schwarz TL
DOI：
10.1073/pnas.96.24.13726
发表时间：
1999-11-23
影响因子：
11.1
作者：
De La Cruz, EM;Wells, AL;Sweeney, HL
通讯作者：
Sweeney, HL
影响因子：
3.4
作者：
Nelson, Shane R.;Ali, M. Yusuf;Warshaw, David M.
通讯作者：
Warshaw, David M.
影响因子：
64.8
作者：
Kerssemakers, Jacob W. J.;Munteanu, E. Laura;Dogterom, Marileen
通讯作者：
Dogterom, Marileen