Centre for Orthopaedic Research, Medical School, The University of Western Australia, Nedlands, WA, 6009, Australia.
Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Signal Transduct Target Ther. 2024 May 15;9(1):124. doi: 10.1038/s41392-024-01839-8.
Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation and disease progression. Particularly, mitochondrial dysfunctions are identified in many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. However, the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among the most important therapeutic targets. In recent years, strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials. Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria, has shown promise in preclinical trials of various diseases. Mitochondrial components, including mtDNA, mitochondria-located microRNA, and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries. Here, we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases. We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies, as well as the clinical translational situation of related pharmacology agents. Finally, this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.
线粒体拥有复杂的功能和信息处理网络,在健康调节和疾病进展中起着关键作用。特别是,线粒体功能障碍在许多常见疾病中都有发现,包括心血管疾病、神经退行性疾病、代谢综合征和癌症。然而,线粒体功能障碍的多面性和难以捉摸的表型阈值使我们难以理解它们对疾病的贡献。尽管如此,这些复杂性并没有阻止线粒体成为最重要的治疗靶点之一。近年来,针对线粒体功能障碍的策略不断涌现并进入临床试验。在各种疾病的临床前试验中,使用健康线粒体来补充或替换受损线粒体等先进干预措施显示出了前景。线粒体的组成部分,包括 mtDNA、位于线粒体的 microRNA 和相关蛋白,可以作为增强免疫代谢疾病和组织损伤中线粒体功能的潜在治疗剂。在这里,我们以常见疾病的具体例子来回顾线粒体病理生理学的现有知识。我们还从饮食补充和靶向治疗的角度总结了目前治疗线粒体功能障碍的策略,以及相关药理学制剂的临床转化情况。最后,本综述讨论了线粒体移植作为一种先进而有前途的治疗方法的创新和潜在应用。