Mitochondrial homeostasis and redox status in cardiovascular diseases: Protective role of the vagal system.
Mitochondrial homeostasis and redox status in cardiovascular diseases: Protective role of the vagal system.
复制标题
心血管疾病中的线粒体稳态和氧化还原状态：迷走神经系统的保护作用。
DOI：
10.1016/j.freeradbiomed.2021.12.255
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发表时间：
2021-12
影响因子：
7.4
通讯作者：
Xi He;Jian-kang Liu;W. Zang
中科院分区：
文献类型：
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作者：
Xi He;Jian-kang Liu;W. Zang
线粒体参与基本的细胞功能，包括能量产生、代谢、氧化还原稳态调节、细胞内Ca 2+处理、凋亡和细胞命运决定。在病理条件下线粒体稳态的破坏导致线粒体活性氧（ROS）的产生和能量不足，这进一步在有害循环中破坏线粒体和细胞的稳态。因此，线粒体氧化还原状态已成为治疗心血管疾病的潜在靶点。在这篇综述中，我们强调了最近的进展，在确定线粒体过程中的作用，在调节线粒体氧化还原状态，包括线粒体动力学（融合-裂变途径），线粒体嵴重塑，线粒体自噬，生物发生，和细胞器的相互作用（内质网-细胞器的相互作用，核-细胞器的通信，和脂滴-细胞器的相互作用）。激活迷走神经系统的策略包括直接迷走激活（迷走神经电刺激和迷走神经递质乙酰胆碱的施用）和药物调节（胆碱和胆碱酯酶抑制剂）。迷走神经系统通过促进线粒体的生物发生和自噬、调节线粒体的融合和分裂、增强线粒体嵴的稳定性、调节线粒体-细胞器的相互作用以及抑制线粒体Ca 2+超载，在维持线粒体内环境稳定和抑制线粒体氧化应激中发挥重要作用。因此，增强迷走神经活性可以维持线粒体的稳态，并代表了一种有前途的心血管疾病的治疗策略。
Mitochondria participate in essential cellular functions, including energy production, metabolism, redox homeostasis regulation, intracellular Ca2+handling, apoptosis, and cell fate determination. Disruption of mitochondrial homeostasis under pathological conditions results in mitochondrial reactive oxygen species (ROS) generation and energy insufficiency, which further disturb mitochondrial and cellular homeostasis in a deleterious loop. Mitochondrial redox status has therefore become a potential target for therapy against cardiovascular diseases. In this review, we highlight recent progress in determining the roles of mitochondrial processes in regulating mitochondrial redox status, including mitochondrial dynamics (fusion–fission pathways), mitochondrial cristae remodeling, mitophagy, biogenesis, and mitochondrion–organelle interactions (endoplasmic reticulum–mitochondrion interactions, nucleus–mitochondrion communication, and lipid droplet–mitochondrion interactions). The strategies that activate vagal system include direct vagal activation (electrical vagal stimulation and administration of vagal neurotransmitter acetylcholine) and pharmacological modulation (choline and cholinesterase inhibitors). The vagal system plays an important role in maintaining mitochondrial homeostasis and suppressing mitochondrial oxidative stress by promoting mitochondrial biogenesis and mitophagy, moderating mitochondrial fusion and fission, strengthening mitochondrial cristae stabilization, regulating mitochondrion–organelle interactions, and inhibiting mitochondrial Ca2+overload. Therefore, enhancement of vagal activity can maintain mitochondrial homeostasis and represents a promising therapeutic strategy for cardiovascular diseases.