Department of Life Sciences, College of Health Sciences and Technology, National Central University, Taoyuan 320317, Taiwan.
Int J Mol Sci. 2023 Jul 31;24(15):12262. doi: 10.3390/ijms241512262.
Mitochondria (MITO) and peroxisomes (PEXO) are the major organelles involved in the oxidative metabolism of cells, but detailed examination of their dynamics and functional adaptations during skeletal muscle (SKM) development (myogenesis) is still lacking. In this study, we found that during myogenesis, MITO DNA, ROS level, and redox ratio increased in myotubes, but the membrane potential (Δψm) and ATP content reduced, implying that the MITO efficiency might reduce during myogenesis. The PEXO number and density both increased during myogenesis, which probably resulted from the accumulation and increased biogenesis of PEXO. The expression of PEXO biogenesis factors was induced during myogenesis in vitro and in utero, and their promoters were also activated by MyoD. Knockdown of the biogenesis factors repressed not only the PEXO density and functions but also the levels of MITO genes and functions, suggesting a close coupling between PEXO biogenesis and MITO functions. Surprisingly, knockdown by the CRISPRi system repressed myogenic differentiation, indicating critical involvement of PEXO biogenesis in myogenesis. Taken together, these observations suggest that the dynamics and functions of both MITO and PEXO are coupled with each other and with the metabolic changes that occur during myogenesis, and these metabolic couplings are critical to myogenesis.
线粒体 (MITO) 和过氧化物酶体 (PEXO) 是参与细胞氧化代谢的主要细胞器，但对它们在骨骼肌 (SKM) 发育 (成肌作用) 过程中的动态和功能适应性的详细研究仍很缺乏。在本研究中，我们发现，在成肌过程中，肌管中的 MITO DNA、ROS 水平和氧化还原比增加，而膜电位 (Δψm) 和 ATP 含量降低，这表明 MITO 效率可能在成肌过程中降低。PEXO 的数量和密度在成肌过程中均增加，这可能是由于 PEXO 的积累和生物发生增加所致。体外和成体内的成肌过程中，PEXO 生物发生因子的表达被诱导，其启动子也被 MyoD 激活。生物发生因子的敲低不仅抑制了 PEXO 的密度和功能，也抑制了 MITO 基因和功能的水平，这表明 PEXO 生物发生与 MITO 功能之间存在紧密的偶联。令人惊讶的是，CRISPRi 系统的敲低抑制了成肌分化，表明 PEXO 生物发生对成肌作用至关重要。总之，这些观察结果表明，MITO 和 PEXO 的动态和功能彼此之间以及与成肌过程中发生的代谢变化相关联，这些代谢偶联对成肌作用至关重要。
