Despite the fact that deregulated NLRP3 inflammasome activation contributes to the pathogenesis of chronic inflammatory or metabolic disorders, the underlying mechanism by which NLRP3 inflammasome signaling is initiated or potentiated remains poorly understood. Much attention is being paid to mitochondria as a regulator of NLRP3 inflammasome activation, but little is known about the role of mitochondrial dynamics for the inflammasome pathway. Here, we present evidence that aberrant mitochondrial elongation caused by the knockdown of dynamin-related protein 1 (Drp1) lead to a marked increase in NLRP3-dependent caspase-1 activation and interleukin-1-beta secretion in mouse bone marrow-derived macrophages. Conversely, carbonyl cyanide m-chlorophenyl hydrazone, a chemical inducer of mitochondrial fission, clearly attenuated NLRP3 inflammasome assembly and activation. Augmented activation of NLRP3 inflammasome by mitochondrial elongation is not resulted from the increased mitochondrial damages of Drp1-knockdown cells. Notably, enhanced extracellular signal-regulated kinase (ERK) signaling in Drp1-knockdown macrophages is implicated in the potentiation of NLRP3 inflammasome activation, possibly via mediating mitochondrial localization of NLRP3 to facilitate the assembly of NLRP3 inflammasome. Taken together, our results provide a molecular insight into the importance of mitochondrial dynamics in potentiating NLRP3 inflammasome activation, leading to aberrant inflammation.

Background: Mitochondrial dysfunction is considered crucial for triggering NLRP3 inflammasome activation. Results: Rotenone-induced impairment of mitochondrial electron transport chain promotes NLRP3 inflammasome activation exclusively with ATP but not with other NLRP3-activating stimulators. Conclusion: High-grade mROS and hyperpolarization are essential for NLRP3 inflammasome activation upon rotenoneinduced mitochondrial dysfunction. Significance: Mitochondrial impairment may selectively prime NLRP3 inflammasome activation, leading to many degenerative diseases.

Exercise is recommended to increase physical health and performance. However, it is unclear how low-intensity exercise (LIE) of different durations may affect or improve recovery ability. This study aimed to investigate how LIE-duration with the same volume affects recovery ability in adults. Twenty healthy male adults participated in this study. Participants were randomly assigned to the 30-min (n = 10) or the 1-h LIE group (n = 10). The intervention included sixteen exercise sessions/four weeks with a 30-min LIE group, and eight exercise sessions/four weeks with a 1-h LIE group. Heart rate (HR) corresponding to <2 mmol∙L−1 blood lactate (La−) was controlled for LIE. Pre- and post-testing was conducted before and after 4-week LIE and tests included jogging/running speed (S), HR, and differences (delta; ∆) in HR and S between pre- and post-testing at 1.5, 2.0, and 4.0 mmol∙L−1 La−. Only the HR at 2.0 mmol∙L−1 La− of the 30-min LIE group was decreased in the post-test compared to the pre-test (p = 0.043). The jogging/running speed of the 1-h LIE group was improved in the post-test compared to the pre-test (p < 0.001, p = 0.006, p = 0.002, respectively). ∆HR at 2.0 and ∆S between the 30-min and 1-h LIE group at 1.5, 2.0, and 4.0 mmol∙L−1 La− were significantly different (p = 0.023, p < 0.001, p = 0.002, and p = 0.019, respectively). Furthermore, moderate to high positive correlations between ∆HR and ∆S of all subjects at 1.5 (r = 0.77), 2.0 (r = 0.77), and 4.0 (r = 0.64) mmol∙L−1 La− were observed. The 1-h LIE group showed improved endurance not only in the low-intensity exercise domain, but also in the beginning of the moderate to high-intensity exercise domain while the 30-min LIE group was not affected by the 4-week LIE intervention. Therefore, LIE (<2.0 mmol∙L−1) for at least 1-h, twice a week, for 4 weeks is suggested to improve recovery ability in adults.

Hypoxia has been shown to promote inflammation, including the release of proinflammatory cytokines, but it is poorly investigated how hypoxia directly affects inflammasome signaling pathways. To explore whether hypoxic stress modulates inflammasome activity, we examined the effect of cobalt chloride (CoCl2)-induced hypoxia on caspase-1 activation in primary mixed glial cultures of the neonatal mouse brain. Unexpectedly, hypoxia induced by oxygen-glucose deprivation or CoCl2 treatment failed to activate caspase-1 in microglial BV-2 cells and primary mixed glial cultures. Of particular interest, CoCl2-induced hypoxic condition considerably inhibited NLRP3-dependent caspase-1 activation in mixed glial cells, but not in bone marrow-derived macrophages. CoCl2-mediated inhibition of NLRP3 inflammasome activity was also observed in the isolated brain microglial cells, but CoCl2 did not affect poly dA:dT-triggered AIM2 inflammasome activity in mixed glial cells. Our results collectively demonstrate that CoCl2-induced hypoxia may negatively regulate NLRP3 inflammasome signaling in brain glial cells, but its physiological significance remains to be determined.

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