National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Nat Commun. 2022 Nov 4;13(1):6622. doi: 10.1038/s41467-022-34445-9.
Mitochondrial networks provide coordinated energy distribution throughout muscle cells. However, pathways specifying mitochondrial networks are incompletely understood and it is unclear how they might affect contractile fiber-type. Here, we show that natural energetic demands placed on Drosophila melanogaster muscles yield native cell-types among which contractile and mitochondrial network-types are regulated differentially. Proteomic analyses of indirect flight, jump, and leg muscles, together with muscles misexpressing known fiber-type specification factor salm, identified transcription factors H15 and cut as potential mitochondrial network regulators. We demonstrate H15 operates downstream of salm regulating flight muscle contractile and mitochondrial network-type. Conversely, H15 regulates mitochondrial network configuration but not contractile type in jump and leg muscles. Further, we find that cut regulates salm expression in flight muscles and mitochondrial network configuration in leg muscles. These data indicate cell type-specific regulation of muscle mitochondrial network organization through evolutionarily conserved transcription factors cut, salm, and H15.
线粒体网络为肌肉细胞提供协调的能量分布。然而，指定线粒体网络的途径还不完全清楚，也不清楚它们如何影响收缩纤维类型。在这里，我们表明，黑腹果蝇肌肉所承受的自然能量需求产生了天然的细胞类型，其中收缩和线粒体网络类型的调节是不同的。间接飞行、跳跃和腿部肌肉的蛋白质组学分析，以及表达已知纤维类型特异性因子 salm 的肌肉，鉴定出转录因子 H15 和 cut 作为潜在的线粒体网络调节剂。我们证明 H15 作为 salm 的下游因子调节飞行肌的收缩和线粒体网络类型。相反，H15 在跳跃和腿部肌肉中调节线粒体网络的结构，但不调节收缩类型。此外，我们发现 cut 调节飞行肌肉中的 salm 表达和腿部肌肉中的线粒体网络结构。这些数据表明，通过进化保守的转录因子 cut、salm 和 H15，对肌肉线粒体网络组织进行细胞类型特异性调节。
