线粒体自噬:肌少-骨质疏松症治疗新靶点
Mitophagy: A novel therapeutic target for osteosarcopenia
  
DOI:10.3969/j.issn.1006-7108.2026.02.024
中文关键词:  线粒体自噬  肌少症  骨质疏松症  肌少-骨质疏松症
英文关键词:mitophagy  sarcopenia  osteoporosis  osteosarcopenia
基金项目:甘肃省高校产业支撑计划项目(2025CYZC-051);兰州市科技计划项目(2023-2-83);兰州市城关区人才创新创业项目(2023-rc-7)
作者单位
马欣1 李宁1 董万涛2* 巩彦龙2 刘婷婷1 1.甘肃中医药大学,甘肃 兰州 730000 2.甘肃中医药大学附属医院,甘肃 兰州 730020 
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中文摘要:
      线粒体自噬作为一种关键细胞质量控制机制,在维持肌肉与骨骼健康中发挥重要作用。该文系统综述了线粒体自噬在肌少症(sarcopenia,SP)和骨质疏松症(osteoporosis,OP)中的分子调控机制,重点分析了BNIP3、PINK1-Parkin信号通路、AMPK/ULK1信号轴以及Sirtuins家族在调控线粒体自噬中的作用。这些通路通过清除功能障碍的线粒体、维持能量代谢稳态以及缓解氧化应激,直接调控肌肉与骨骼的生理功能。在肌少-骨质疏松症(osteosarcopenia,OS)中,线粒体自噬的紊乱可能加速肌肉与骨骼的退行性改变,从而显著增加跌倒及骨折的发生率。尽管已有研究揭示了线粒体自噬在SP和OP中的重要性,但其在OS中的作用仍处于初步探索阶段。未来的研究应进一步深入探讨线粒体自噬在OS中的具体分子机制,尤其是其在肌肉与骨骼相互作用中的调控功能。此外,开发针对线粒体自噬的干预策略,例如通过药物或基因治疗手段增强线粒体自噬活性,可能为SP、OP及OS的治疗开辟新途径。通过整合多组学技术与动物模型,深入研究线粒体自噬的分子网络及其在肌肉骨骼系统中的动态调节机制,将有助于揭示这些疾病的病理生理基础,为临床治疗提供坚实的理论依据。总之,线粒体自噬作为连接肌肉与骨骼健康的核心分子机制,其深入研究不仅能够深化对SP、OP及OS发病机制的理解,还可能为开发创新性治疗策略提供重要的科学线索。
英文摘要:
      Mitophagy, crucial for cell quality control, is vital for muscle and bone health. This review explores its molecular mechanisms in sarcopenia (SP) and osteoporosis (OP), focusing on BNIP3, the PINK1-Parkin pathway, the AMPK/ULK1 axis, and Sirtuins family. These pathways maintain muscle and bone function by removing damaged mitochondria, stabilizing energy metabolism, and reducing oxidative stress. In osteosarcopenia (OS), mitophagy disruption may hasten muscle and bone degeneration and increase fracture risks. While mitophagy's role in SP and OP is established, its function in OS remains largely unexplored. Future research should delve into mitophagy's specific mechanisms in OS, particularly its regulatory role in muscle-bone interactions. Developing mitophagy-targeted interventions, like pharmacological or gene therapies to enhance mitophagy activity, could open new treatment avenues for SP, OP, and OS. Integrating multi-omics and animal models to study mitophagy's molecular networks and dynamic regulation in the musculoskeletal system may reveal these diseases' pathological bases, offering solid theoretical grounds for clinical therapy. In summary, the study of mitophagy, central to muscle and bone health, may deepen our understanding of SP, OP, and OS pathogenesis and provide clues for innovative treatments.
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