Liu Jiliu, Wang Junyi, Xiong Anying, Zhang Lei, Zhang Yi, Liu Yao, Xiong Ying, Li Guoping, He Xiang
Laboratory of Allergy and Precision Medicine, School of Medicine, Southwest Jiaotong University, Chengdu Institute of Respiratory Health, The Third People's Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, China.
Department of Pulmonary and Critical Care Medicine, Chengdu Third People's Hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu, China.
Front Physiol. 2023 Jul 19;14:1236651. doi: 10.3389/fphys.2023.1236651. eCollection 2023.
Lung diseases are a major global health problem, affecting millions of people worldwide. Recent research has highlighted the critical role that mitochondrial quality control plays in respiratory-related diseases, including chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). In this review, we summarize recent findings on the involvement of mitochondrial quality control in these diseases and discuss potential therapeutic strategies. Mitochondria are essential organelles for energy production and other cellular processes, and their dysfunction is associated with various diseases. The quality control of mitochondria involves a complex system of pathways, including mitophagy, mitochondrial biogenesis, fusion/fission dynamics, and regulation of gene expression. In COPD and lung cancer, mitochondrial quality control is often involved in disease development by influencing oxidative stress and apoptosis. In IPF, it appears to be involved in the disease process by participating in the cellular senescence process. Mitochondrial quality control is a promising target for therapeutic interventions in lung diseases. However, there are conflicting reports on different pathological processes, such as the role of mitochondrial autophagy in lung cancer, which pose difficulties in the study of targeted mitochondrial quality control drugs. Additionally, there seems to be a delicate balance between the mitochondrial quality control processes in the physiological state. Emerging evidence suggests that molecules such as PTEN-induced putative kinase 1 (PINK1), parkin RBR E3 ubiquitin protein ligase (PRKN), dynamin-related protein 1 (DRP1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), as well as the signaling pathways they affect, play an important role in respiratory-related diseases. Targeting these molecules and pathways could contribute to the development of effective treatments for lung diseases. In conclusion, the involvement of mitochondrial quality control in lung diseases presents a promising new avenue for disease treatment. Further research is needed to better understand the complex mechanisms involved in the pathogenesis of respiratory diseases and to develop targeted therapies that could improve clinical outcomes.
肺部疾病是一个重大的全球健康问题,影响着全球数百万人。最近的研究突出了线粒体质量控制在包括慢性阻塞性肺疾病(COPD)、肺癌和特发性肺纤维化(IPF)在内的呼吸道相关疾病中所起的关键作用。在本综述中,我们总结了线粒体质量控制参与这些疾病的最新研究结果,并讨论了潜在的治疗策略。线粒体是能量产生和其他细胞过程所必需的细胞器,其功能障碍与多种疾病相关。线粒体质量控制涉及一个复杂的通路系统,包括线粒体自噬、线粒体生物合成、融合/分裂动态以及基因表达调控。在COPD和肺癌中,线粒体质量控制常常通过影响氧化应激和细胞凋亡参与疾病发展。在IPF中,它似乎通过参与细胞衰老过程而涉及疾病进程。线粒体质量控制是肺部疾病治疗干预的一个有前景的靶点。然而,关于不同病理过程存在相互矛盾的报道,比如线粒体自噬在肺癌中的作用,这给靶向线粒体质量控制药物的研究带来了困难。此外,生理状态下的线粒体质量控制过程之间似乎存在微妙的平衡。新出现的证据表明,诸如PTEN诱导的假定激酶1(PINK1)、帕金RBR E3泛素蛋白连接酶(PRKN)、动力相关蛋白1(DRP1)和过氧化物酶体增殖物激活受体γ共激活因子1α(PGC1-α)等分子以及它们所影响的信号通路在呼吸道相关疾病中起重要作用。针对这些分子和通路可能有助于开发有效的肺部疾病治疗方法。总之,线粒体质量控制参与肺部疾病为疾病治疗提供了一个有前景的新途径。需要进一步研究以更好地理解呼吸道疾病发病机制中涉及的复杂机制,并开发能够改善临床结果的靶向治疗方法。