Myo19-flox Mouse

Myo19, a member of a novel class of myosin, is an actin-based motor that has a crucial role in mitochondrial homeostasis. It is associated with pathways related to mitochondrial dynamics, such as fission and fusion, and is important for maintaining mitochondrial function and cellular processes like cell division. Genetic models, especially knockout models, can be valuable for studying its functions [2,3,7].

In Myo19-deficient HEK293T cells, mitochondria were not properly fragmented during mitosis and were asymmetrically partitioned to daughter cells. Respiratory functions of mitochondria were impaired, ROS generation was enhanced, and cell proliferation, cytokinesis, and cell-matrix adhesion were negatively affected. Myo19 also regulates focal adhesions in interphase, and mitochondrial fusion and mitochondrially associated levels of fission protein Drp1 and adaptor proteins dynactin and TRAK1 at prometaphase [6].

Myo19 knockdown in other cell systems induced mitochondrial elongation, while overexpression induced fragmentation. This fragmentation was blocked by a Myo19 mutation predicted to inhibit ATPase activity and strong actin binding. Myo19-driven fragmentation was blocked by depletion of either the CAAX splice variant of the endoplasmic reticulum-anchored formin INF2 or the mitochondrially localized F-actin nucleator Spire1C, suggesting that Myo19 promotes fission by stabilizing mitochondria-ER contacts [1].

Loss of Myo19 in some studies enhanced the microenvironmental ROS gradient and chemotaxis, increasing tumor metastasis [4]. Also, depletion of Myo19 or disruption of its motor activity led to altered mitochondria membrane potential and decreased oxidative phosphorylation (OXPHOS), as it is critical for maintaining cristae structure by associating with the SAM-MICOS super complex [5].

In conclusion, Myo19 is essential for mitochondrial fission, proper mitochondrial partitioning during cell division, maintaining cristae structure for OXPHOS, and preventing enhanced tumor metastasis by regulating the microenvironmental ROS gradient. The use of Myo19-deficient models has significantly contributed to understanding its role in these biological processes and disease-related conditions, providing insights into potential therapeutic targets for diseases associated with mitochondrial dysfunction and cancer metastasis.