摘要
线粒体作为细胞的“能量工厂”和信号转导枢纽，其功能完整性对维持细胞稳态至关重要。近年的前沿研究表明，线粒体功能异常，包括氧化磷酸化缺陷、活性氧过度产生、线粒体动力学（融合/分裂）失衡、线粒体自噬障碍以及线粒体DNA突变等，远非仅导致经典的线粒体病，而是广泛参与并驱动了众多重大人类疾病的发生与发展。本综述系统总结了线粒体功能异常的核心分子机制，重点阐述了其在代谢性疾病（如糖尿病及其心肾并发症）、神经退行性疾病、自身免疫性疾病、肿瘤以及肌肉骨骼疾病等中的关键作用。研究揭示，线粒体通过释放损伤相关分子模式（如mtDNA）激活固有免疫（如cGAS-STING通路），通过内质网-线粒体紧密互作协调应激反应，并通过非编码RNA进行精细的表观遗传调控，从而深度介入疾病病理网络。在诊疗策略方面，新兴的线粒体靶向探针、线粒体功能活体检测、基于细胞外囊泡的线粒体转移技术以及针对线粒体自噬、动力学和特定蛋白（如Metadherin, TIPE1）的干预手段，为相关疾病的精准诊断和治疗提供了全新视角。传统中医药也在调控线粒体稳态方面展现出独特潜力。总之，线粒体已成为理解疾病共性病理生理机制和开发新型疗法的核心靶标，未来研究需进一步整合多组学与前沿技术，推动线粒体医学向临床转化。
关键词： 线粒体；线粒体功能障碍；代谢疾病；神经退行性疾病；线粒体自噬；细胞器间通讯
Abstract
Mitochondria, as the "energy factories" of cells and hubs for signal transduction, play a crucial role in maintaining cellular homeostasis. Cutting-edge research in recent years has shown that mitochondrial dysfunction, including defects in oxidative phosphorylation, excessive production of reactive oxygen species, imbalance in mitochondrial dynamics (fusion/fission), impaired mitochondrial autophagy, and mitochondrial DNA mutations, is far from merely causing classic mitochondrial diseases. Instead, it is widely involved in and drives the occurrence and development of numerous major human diseases. This review systematically summarizes the core molecular mechanisms of mitochondrial dysfunction, with a focus on its key role in various diseases, such as metabolic disorders (e.g., diabetes and its cardiorenal complications), neurodegenerative diseases, autoimmune diseases, tumors, and musculoskeletal diseases. Studies reveal that mitochondria deeply engage in disease pathological networks by releasing damage-associated molecular patterns (such as mtDNA) to activate innate immunity (such as the cGAS-STING pathway), coordinating stress responses through endoplasmic reticulum-mitochondria tight interaction, and performing fine epigenetic regulation through non-coding RNAs. In terms of diagnostic and therapeutic strategies, emerging mitochondrial-targeting probes, in vivo mitochondrial function detection, extracellular vesicle-based mitochondrial transfer techniques, and intervention methods targeting mitochondrial autophagy, dynamics, and specific proteins (such as Metadherin, TIPE1) provide new perspectives for the precise diagnosis and treatment of related diseases. Traditional Chinese medicine also shows unique potential in regulating mitochondrial homeostasis. In summary, mitochondria have become a core target for understanding common pathological physiological mechanisms of diseases and developing novel therapies. Future research needs to further integrate multi-omics and cutting-edge technologies to advance mitochondrial medicine towards clinical translation.
Key words： Mitochondria; Mitochondrial dysfunction; Metabolic diseases; Neurodegenerative diseases; Mitochondrial autophagy; Interorganelle communication
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