Pang Brian Pak Shing, Chan Wing Suen, Chan Chi Bun
School of Biological Sciences, The University of Hong Kong, Hong Kong.
Antioxidants (Basel). 2021 Jan 27;10(2):179. doi: 10.3390/antiox10020179.
Mitochondria are the cellular powerhouses that generate adenosine triphosphate (ATP) to substantiate various biochemical activities. Instead of being a static intracellular structure, they are dynamic organelles that perform constant structural and functional remodeling in response to different metabolic stresses. In situations that require a high ATP supply, new mitochondria are assembled (mitochondrial biogenesis) or formed by fusing the existing mitochondria (mitochondrial fusion) to maximize the oxidative capacity. On the other hand, nutrient overload may produce detrimental metabolites such as reactive oxidative species (ROS) that wreck the organelle, leading to the split of damaged mitochondria (mitofission) for clearance (mitophagy). These vital processes are tightly regulated by a sophisticated quality control system involving energy sensing, intracellular membrane interaction, autophagy, and proteasomal degradation to optimize the number of healthy mitochondria. The effective mitochondrial surveillance is particularly important to skeletal muscle fitness because of its large tissue mass as well as its high metabolic activities for supporting the intensive myofiber contractility. Indeed, the failure of the mitochondrial quality control system in skeletal muscle is associated with diseases such as insulin resistance, aging, and muscle wasting. While the mitochondrial dynamics in cells are believed to be intrinsically controlled by the energy content and nutrient availability, other upstream regulators such as hormonal signals from distal organs or factors generated by the muscle itself may also play a critical role. It is now clear that skeletal muscle actively participates in systemic energy homeostasis via producing hundreds of myokines. Acting either as autocrine/paracrine or circulating hormones to crosstalk with other organs, these secretory myokines regulate a large number of physiological activities including insulin sensitivity, fuel utilization, cell differentiation, and appetite behavior. In this article, we will review the mechanism of myokines in mitochondrial quality control and ROS balance, and discuss their translational potential.
线粒体是细胞的动力源，可生成三磷酸腺苷（ATP）以维持各种生化活动。它们并非静态的细胞内结构，而是动态细胞器，会根据不同的代谢应激进行持续的结构和功能重塑。在需要大量ATP供应的情况下，新的线粒体通过组装（线粒体生物发生）或现有线粒体融合（线粒体融合）形成，以最大化氧化能力。另一方面，营养过剩可能产生有害代谢物，如活性氧化物质（ROS），这些物质会破坏细胞器，导致受损线粒体分裂（线粒体分裂）以便清除（线粒体自噬）。这些重要过程受到一个复杂的质量控制系统的严格调控，该系统涉及能量感知、细胞内膜相互作用、自噬和蛋白酶体降解，以优化健康线粒体的数量。有效的线粒体监测对骨骼肌健康尤为重要，因为骨骼肌组织量大，且具有高代谢活性以支持强烈的肌纤维收缩。事实上，骨骼肌中线粒体质量控制系统的失效与胰岛素抵抗、衰老和肌肉萎缩等疾病有关。虽然细胞中的线粒体动态被认为本质上受能量含量和营养可用性控制，但其他上游调节因子，如来自远端器官的激素信号或肌肉自身产生的因子，也可能起关键作用。现在很清楚，骨骼肌通过产生数百种肌动蛋白，积极参与全身能量稳态。这些分泌性肌动蛋白作为自分泌/旁分泌或循环激素与其他器官相互作用，调节大量生理活动，包括胰岛素敏感性、燃料利用、细胞分化和食欲行为。在本文中，我们将综述肌动蛋白在线粒体质量控制和ROS平衡中的机制，并讨论它们的转化潜力。
