Department of Clinical and Molecular Sciences, Marche Polytechnic University, Ancona, Italy.
Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Nat Rev Immunol. 2023 Mar;23(3):159-173. doi: 10.1038/s41577-022-00760-x. Epub 2022 Jul 25.
Numerous mitochondrial constituents and metabolic products can function as damage-associated molecular patterns (DAMPs) and promote inflammation when released into the cytosol or extracellular milieu. Several safeguards are normally in place to prevent mitochondria from eliciting detrimental inflammatory reactions, including the autophagic disposal of permeabilized mitochondria. However, when the homeostatic capacity of such systems is exceeded or when such systems are defective, inflammatory reactions elicited by mitochondria can become pathogenic and contribute to the aetiology of human disorders linked to autoreactivity. In addition, inefficient inflammatory pathways induced by mitochondrial DAMPs can be pathogenic as they enable the establishment or progression of infectious and neoplastic disorders. Here we discuss the molecular mechanisms through which mitochondria control inflammatory responses, the cellular pathways that are in place to control mitochondria-driven inflammation and the pathological consequences of dysregulated inflammatory reactions elicited by mitochondrial DAMPs.
许多线粒体成分和代谢产物可以作为损伤相关分子模式（DAMPs）发挥作用，当它们被释放到细胞质或细胞外环境中时，会促进炎症反应。通常有几种保护机制来防止线粒体引发有害的炎症反应，包括自噬性处理通透性线粒体。然而，当这些系统的稳态能力超过或当这些系统有缺陷时，线粒体引发的炎症反应可能会变得具有致病性，并导致与自身反应相关的人类疾病的发病机制。此外，线粒体 DAMPs 诱导的无效炎症途径也可能具有致病性，因为它们能够建立或促进感染性和肿瘤性疾病的发展。在这里，我们讨论了线粒体控制炎症反应的分子机制、控制线粒体驱动的炎症的细胞途径以及线粒体 DAMPs 引发的失调炎症反应的病理后果。
