Marques Eloïse, Kramer Robbin, Ryan Dylan G
MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.
NPJ Metab Health Dis. 2024;2(1):6. doi: 10.1038/s44324-024-00008-3. Epub 2024 May 27.
The ability of mitochondria to transform the energy we obtain from food into cell phosphorylation potential has long been appreciated. However, recent decades have seen an evolution in our understanding of mitochondria, highlighting their significance as key signal-transducing organelles with essential roles in immunity that extend beyond their bioenergetic function. Importantly, mitochondria retain bacterial motifs as a remnant of their endosymbiotic origin that are recognised by innate immune cells to trigger inflammation and participate in anti-microbial defence. This review aims to explore how mitochondrial physiology, spanning from oxidative phosphorylation (OxPhos) to signalling of mitochondrial nucleic acids, metabolites, and lipids, influences the effector functions of phagocytes. These myriad effector functions include macrophage polarisation, efferocytosis, anti-bactericidal activity, antigen presentation, immune signalling, and cytokine regulation. Strict regulation of these processes is critical for organismal homeostasis that when disrupted may cause injury or contribute to disease. Thus, the expanding body of literature, which continues to highlight the central role of mitochondria in the innate immune system, may provide insights for the development of the next generation of therapies for inflammatory diseases.
线粒体将我们从食物中获取的能量转化为细胞磷酸化电位的能力早已为人所知。然而，近几十年来，我们对线粒体的理解发生了演变，突出了它们作为关键信号转导细胞器的重要性，其在免疫中的重要作用超出了它们的生物能量功能。重要的是，线粒体保留了细菌基序，作为其共生起源的残余物，先天免疫细胞可识别这些基序以触发炎症并参与抗菌防御。本综述旨在探讨线粒体生理学，从氧化磷酸化（OxPhos）到线粒体核酸、代谢物和脂质的信号传导，如何影响吞噬细胞的效应器功能。这些众多的效应器功能包括巨噬细胞极化、胞葬作用、抗菌活性、抗原呈递、免疫信号传导和细胞因子调节。对这些过程的严格调节对于机体稳态至关重要，一旦破坏可能会导致损伤或引发疾病。因此，不断涌现的大量文献继续强调线粒体在先天免疫系统中的核心作用，这可能为开发下一代炎症性疾病治疗方法提供见解。
