Myo19-KO Mouse

Myo19, a mitochondrially localized myosin, is crucial for mitochondrial homeostasis as it promotes mitochondrial fission by tethering mitochondria to endoplasmic reticulum-associated actin [1]. It is also involved in mitochondrial movement, dynamics, and positioning, and impacts cell function through its effects on mitochondria [2,3]. Myo19 has a unique evolutionary history and is an actin-activated ATPase [2].

Myo19 knockdown led to mitochondrial elongation, while overexpression induced fragmentation [1]. In Myo19-deficient HEK293T cells, mitochondria were not properly fragmented at mitosis, and were partitioned asymmetrically to daughter cells. Respiratory functions were impaired, ROS generation was enhanced, and cell proliferation, cytokinesis, and cell-matrix adhesion were negatively affected [5]. Myo19 silencing in cells also caused defects in mitochondrial distribution within cells and during division, and some cells underwent stochastic division failure [6]. Loss of Myo19 enhanced the microenvironmental ROS gradient, promoting tumor cell chemotaxis and metastasis [4].

In conclusion, Myo19 is essential for maintaining mitochondrial dynamics, including fission, and for proper mitochondrial inheritance during cell division. Its loss is associated with abnormal mitochondrial functions and increased tumor metastasis, highlighting its significance in normal cellular processes and disease, especially in understanding the role of mitochondria in cancer metastasis.

References:

1. Coscia, Stephen M, Thompson, Cameron P, Tang, Qing, Lakadamyali, Melike, Holzbaur, Erika L F. 2023. Myo19 tethers mitochondria to endoplasmic reticulum-associated actin to promote mitochondrial fission. In Journal of cell science, 136, . doi:10.1242/jcs.260612. https://pubmed.ncbi.nlm.nih.gov/36744380/

2. Bocanegra, Jennifer L, Adikes, Rebecca, Quintero, Omar A. . Myosin XIX. In Advances in experimental medicine and biology, 1239, 439-451. doi:10.1007/978-3-030-38062-5_20. https://pubmed.ncbi.nlm.nih.gov/32451871/

3. Shneyer, Boris I, Ušaj, Marko, Henn, Arnon. 2015. Myo19 is an outer mitochondrial membrane motor and effector of starvation-induced filopodia. In Journal of cell science, 129, 543-56. doi:10.1242/jcs.175349. https://pubmed.ncbi.nlm.nih.gov/26659663/

4. Ren, Xiaoyu, Shi, Peng, Su, Jing, Hu, Yiping, Wu, Congying. 2024. Loss of Myo19 increases metastasis by enhancing microenvironmental ROS gradient and chemotaxis. In EMBO reports, 25, 971-990. doi:10.1038/s44319-023-00052-y. https://pubmed.ncbi.nlm.nih.gov/38279020/

5. Majstrowicz, Katarzyna, Honnert, Ulrike, Nikolaus, Petra, Hemkemeyer, Sandra A, Bähler, Martin. 2021. Coordination of mitochondrial and cellular dynamics by the actin-based motor Myo19. In Journal of cell science, 134, . doi:10.1242/jcs.255844. https://pubmed.ncbi.nlm.nih.gov/34013964/

6. Rohn, Jennifer L, Patel, Jigna V, Neumann, Beate, Ellenberg, Jan, Baum, Buzz. 2014. Myo19 ensures symmetric partitioning of mitochondria and coupling of mitochondrial segregation to cell division. In Current biology : CB, 24, 2598-605. doi:10.1016/j.cub.2014.09.045. https://pubmed.ncbi.nlm.nih.gov/25447992/