Zmynd17 controls muscle mitochondrial quality and whole‐body metabolism

Abstract

Muscle mitochondria are crucial for systemic metabolic function, yet their regulation remains unclear. The zinc finger MYND domain-containing protein 17 (Zmynd17) was recently identified as a muscle-specific gene in mammals. Here, we investigated the role of Zmynd17 in mice. We found Zmynd17 predominantly expressed in skeletal muscle, especially in fast glycolytic muscle. Genetic Zmynd17 inactivation led to morphologic and functional abnormalities in muscle mitochondria, resulting in decreased respiratory function. Metabolic stress induced by a high-fat diet upregulated Zmynd17 expression and further exacerbated muscle mitochondrial morphology in Zmynd17-deficient mice. Strikingly, Zmynd17 deficiency significantly aggravated metabolic stress-induced hepatic steatosis, glucose intolerance, and insulin resistance. Furthermore, middle-aged mice lacking Zmynd17 exhibited impaired aerobic exercise performance, glucose intolerance, and insulin resistance. Thus, our results indicate that Zmynd17 is a metabolic stress-inducible factor that maintains muscle mitochondrial integrity, with its deficiency profoundly affecting whole-body glucose metabolism.-Fujita, R., Yoshioka, K., Seko, D., Suematsu, T., Mitsuhashi, S., Senoo, N., Miura, S., Nishino, I., Ono, Y. Zmynd17 controls muscle mitochondrial quality and whole-body metabolism.

Genes lost during the transition from land to water in cetaceans highlight genomic changes involved in aquatic adaptations

“…While the loss of these genes highlights differences in the cetacean immune system, it is not clear whether these losses are potentially related to different pathogens encountered in a fullyaquatic environment, changes in gut microbiome composition in these obligate carnivores, or other reasons. Another example is MSS51, a gene that is predominantly expressed in fast glycolytic fibers of skeletal muscle (118). Inactivation of MSS51 in muscle cell lines directs muscle energy metabolism towards beta-oxidation of fatty acids (119).…”

Distinct Roles of Zmynd17 and PGC1α in Mitochondrial Quality Control and Biogenesis in Skeletal Muscle

“…Forelimb grip strength was measured, using a Grip Strength Meter (Columbus Instruments, Columbus, OH, United States) for mice, as previously described with some minor modifications (Fujita et al, 2018). Peak tension [in neuton (N)] was recorded when the mouse released its grip.…”

“…Mice were subjected to a low-intensity, run-to-exhaustion protocol on a motorized treadmill, as previously described (Fujita et al, 2018). Mice were familiarized with the treadmill (Muromachi Kikai, Tokyo, Japan) for 10 min at 10 m/min for 2 consecutive days.…”

“…Electron microscopic examinations were performed as previously described (Fujita et al, 2018). Muscle samples were fixed in 2.5% glutaraldehyde in 0.1M phosphate buffer (pH 7.4), for 4 h at 4 • C. Post-fixation, the samples were incubated with 1% osmium tetroxide for 2 h at 4 • C. Muscle samples were then dehydrated in a graded series of ethanol and embedded in Epon 812.…”

“…We have previously reported that the muscle-specific gene zinc finger MYND domain-containing protein 17 (Zmynd17) controls mitochondrial quality in muscle, especially in fastglycolytic muscles (Fujita et al, 2018). Zmynd17 deletion resulted in abnormal mitochondria in skeletal muscle.…”