Ye Lin, Fu Xinzhi, Li Qi
School of Basic Medicine Qingdao University Qingdao Shandong China.
School of Nursing Qingdao University Qingdao Shandong China.
MedComm (2020). 2025 Aug 15;6(8):e70319. doi: 10.1002/mco2.70319. eCollection 2025 Aug.
Mitochondria are central regulators of cellular energy metabolism, and their functional integrity is essential for maintaining cellular homeostasis. Mitochondrial quality control (MQC) encompasses a coordinated network of mitochondrial biogenesis, dynamics (fusion and fission), and selective autophagy (mitophagy), which together sustain mitochondrial structure and function. Under physiological conditions, MQC ensures the removal of dysfunctional mitochondria, restricts excessive reactive oxygen species production, and modulates apoptosis, thereby supporting the high energy demands of organs such as the heart and brain. Disruption of MQC contributes to the onset and progression of various diseases, including neurodegenerative disorders, cardiovascular pathologies, and metabolic syndromes, largely through accumulation of damaged mitochondria and impaired metabolic signaling. While the core components of MQC have been characterized, the mechanistic interplay among its modules and their disease-specific alterations remain incompletely defined. This review provides an integrated overview of the molecular pathways governing mitochondrial biogenesis, dynamics, and mitophagy, with a focus on their cross-talk in maintaining mitochondrial homeostasis. We further discuss how MQC dysfunction contributes to disease pathogenesis and examine emerging therapeutic approaches aimed at restoring mitochondrial quality. Understanding the regulatory logic of MQC not only elucidates fundamental principles of cellular stress adaptation but also informs novel strategies for disease intervention.
线粒体是细胞能量代谢的核心调节因子,其功能完整性对于维持细胞内稳态至关重要。线粒体质量控制(MQC)涵盖了线粒体生物发生、动力学(融合与分裂)以及选择性自噬(线粒体自噬)的协调网络,这些共同维持着线粒体的结构和功能。在生理条件下,MQC确保清除功能失调的线粒体,限制过量活性氧的产生,并调节细胞凋亡,从而满足心脏和大脑等器官对高能量的需求。MQC的破坏会导致包括神经退行性疾病、心血管疾病和代谢综合征在内的各种疾病的发生和发展,这主要是通过受损线粒体的积累和代谢信号受损实现的。虽然MQC的核心成分已经得到了表征,但其各模块之间的机制相互作用以及它们在疾病中的特异性改变仍未完全明确。本综述对调控线粒体生物发生、动力学和线粒体自噬的分子途径进行了综合概述,重点关注它们在维持线粒体稳态中的相互作用。我们还讨论了MQC功能障碍如何导致疾病发病机制,并研究了旨在恢复线粒体质量的新兴治疗方法。理解MQC的调控逻辑不仅阐明了细胞应激适应的基本原理,也为疾病干预提供了新的策略。