Carbon monoxide (CO) has long been known as a "silent killer" because of its ability to bind hemoglobin (Hb), leading to reduced oxygen carrying capacity of Hb, which is the main cause of CO poisoning (COP) in humans. Emerging studies suggest that mitochondria is a key target of CO action that can impact key biological processes, including apoptosis, cellular proliferation, inflammation, and autophagy. Despite its toxicity at high concentrations, CO also exhibits cyto- and tissue-protective effects at low concentrations in animal models of organ injury and disease. Specifically, CO modulates the production of pro- or anti-inflammatory cytokines and mediators by regulating the NLRP3 inflammasome. Given that human diseases are strongly associated with inflammation, a deep understanding of the exact mechanism is helpful for treatment. Autophagic factors and inflammasomes interact in various situations, including inflammatory disease, and exosomes might function as the bridge between the inflammasome and autophagy activation. Thus, the interplay among autophagy, mitochondrial dysfunction, exosomes, and the inflammasome may play pivotal roles in the health effects of CO. In this review, we summarize the latest research on the beneficial and toxic effects of CO and their underlying mechanisms, focusing on the important role of the inflammasome and its possible crosstalk with autophagy and exosomes. This knowledge may lead to the development of new therapies for inflammation-related diseases and is essential for the development of new therapeutic strategies and biomarkers of COP.
Keywords: Autophagy; Carbon monoxide; Exosome; Mitochondria; NLRP3 inflammasome.