Upon detecting pathogens or cell stress, several NOD-like receptors (NLRs) form inflammasome complexes with the adapter ASC and caspase-1, inducing gasdermin D (GSDMD)-dependent cell death and maturation and release of IL-1β and IL-18. The triggers and activation mechanisms of several inflammasome-forming sensors are not well understood. Here we show that mitochondrial damage activates the NLRP10 inflammasome, leading to ASC speck formation and caspase-1-dependent cytokine release. While the AIM2 inflammasome can also sense mitochondrial demise by detecting mitochondrial DNA (mtDNA) in the cytosol, NLRP10 monitors mitochondrial integrity in an mtDNA-independent manner, suggesting the recognition of distinct molecular entities displayed by the damaged organelles. NLRP10 is highly expressed in differentiated human keratinocytes, in which it can also assemble an inflammasome. Our study shows that this inflammasome surveils mitochondrial integrity. These findings might also lead to a better understanding of mitochondria-linked inflammatory diseases.

在检测到病原体或细胞应激后，几种 NOD 样受体 (NLR) 与衔接子 ASC 和 caspase-1 形成炎性体复合物，诱导 gasdermin D (GSDMD) 依赖性细胞死亡和成熟以及 IL-1β 和 IL-18 的释放。几种炎性小体形成传感器的触发和激活机制尚不清楚。在这里，我们显示线粒体损伤激活 NLRP10 炎性体，导致 ASC 斑点形成和 caspase-1 依赖性细胞因子释放。虽然 AIM2 炎性体还可以通过检测胞质溶胶中的线粒体 DNA (mtDNA) 来感知线粒体死亡，但 NLRP10 以不依赖于 mtDNA 的方式监测线粒体完整性，表明可以识别受损细胞器所显示的不同分子实体。NLRP10 在分化的人角质形成细胞中高表达，它还可以在其中组装一个炎性小体。我们的研究表明，这种炎症小体监视线粒体的完整性。这些发现也可能导致更好地了解线粒体相关的炎症性疾病。