Myo19 tethers mitochondria to endoplasmic reticulum-associated actin to promote mitochondrial fission.

Autor:	Coscia SM; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Cell and Molecular Biology Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Thompson CP; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Tang Q; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Baltrusaitis EE; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Rhodenhiser JA; Department of Biology, University of Richmond, Richmond, VA 23173, USA., Quintero-Carmona OA; Department of Biology, University of Richmond, Richmond, VA 23173, USA., Ostap EM; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Lakadamyali M; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA., Holzbaur ELF; Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.; Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2023 Mar 01; Vol. 136 (5). Date of Electronic Publication: 2023 Mar 02.
DOI:	10.1242/jcs.260612
Abstrakt:	Mitochondrial homeostasis requires a dynamic balance of fission and fusion. The actin cytoskeleton promotes fission, and we found that the mitochondrially localized myosin, myosin 19 (Myo19), is integral to this process. Myo19 knockdown induced mitochondrial elongation, whereas Myo19 overexpression induced fragmentation. This mitochondrial fragmentation was blocked by a Myo19 mutation predicted to inhibit ATPase activity and strong actin binding but not by mutations predicted to affect the working stroke of the motor that preserve ATPase activity. Super-resolution imaging indicated a dispersed localization of Myo19 on mitochondria, which we found to be dependent on metaxins. These observations suggest that Myo19 acts as a dynamic actin-binding tether that facilitates mitochondrial fragmentation. Myo19-driven fragmentation was blocked by depletion of either the CAAX splice variant of the endoplasmic reticulum (ER)-anchored formin INF2 or the mitochondrially localized F-actin nucleator Spire1C (a splice variant of Spire1), which together polymerize actin at sites of mitochondria-ER contact for fission. These observations imply that Myo19 promotes fission by stabilizing mitochondria-ER contacts; we used a split-luciferase system to demonstrate a reduction in these contacts following Myo19 depletion. Our data support a model in which Myo19 tethers mitochondria to ER-associated actin to promote mitochondrial fission. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2023. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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