The article "Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection" by Igor Belenichev et al. explores the multifaceted roles of nitric oxide (•NO) in various physiological and pathological processes. •NO, despite its simple structure, plays a crucial role in cardiovascular function, the central nervous system, reproduction, endocrine regulation, respiration, and digestion. The authors discuss the mechanisms of •NO's cytoprotective actions, such as regulating the expression of antiapoptotic and chaperone proteins and mitochondrial function, as well as its cytotoxic effects, including the initiation of nitrosative and oxidative stresses, production of reactive oxygen and nitrogen species, and involvement in apoptosis and mitosis. The article delves into the synthesis and regulation of •NO, highlighting the roles of nitric oxide synthases (NOS) and the importance of L-arginine. It also examines the mechanisms of •NO cytotoxicity, including the formation of peroxynitrite and the inhibition of oxidative phosphorylation in mitochondria. The authors explore the interaction between •NO and mitochondria, particularly in the context of apoptosis, and the role of mitochondrial nitric oxide synthase (mtNOS) in this process. Additionally, the article discusses the antiapoptotic effects of •NO, such as the induction of heat shock proteins (HSP) and the chaperone-mediated import of precursor proteins into mitochondria. It also reviews the clinical relevance of •NO in conditions like arterial hypertension and cerebral ischemia, emphasizing the balance between •NO and superoxide anions and the impact of the thiol-disulfide system on •NO's properties. Overall, the article provides a comprehensive overview of the complex roles of •NO in health and disease, highlighting the need for further research to understand and modulate its actions for therapeutic purposes.The article "Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection" by Igor Belenichev et al. explores the multifaceted roles of nitric oxide (•NO) in various physiological and pathological processes. •NO, despite its simple structure, plays a crucial role in cardiovascular function, the central nervous system, reproduction, endocrine regulation, respiration, and digestion. The authors discuss the mechanisms of •NO's cytoprotective actions, such as regulating the expression of antiapoptotic and chaperone proteins and mitochondrial function, as well as its cytotoxic effects, including the initiation of nitrosative and oxidative stresses, production of reactive oxygen and nitrogen species, and involvement in apoptosis and mitosis. The article delves into the synthesis and regulation of •NO, highlighting the roles of nitric oxide synthases (NOS) and the importance of L-arginine. It also examines the mechanisms of •NO cytotoxicity, including the formation of peroxynitrite and the inhibition of oxidative phosphorylation in mitochondria. The authors explore the interaction between •NO and mitochondria, particularly in the context of apoptosis, and the role of mitochondrial nitric oxide synthase (mtNOS) in this process. Additionally, the article discusses the antiapoptotic effects of •NO, such as the induction of heat shock proteins (HSP) and the chaperone-mediated import of precursor proteins into mitochondria. It also reviews the clinical relevance of •NO in conditions like arterial hypertension and cerebral ischemia, emphasizing the balance between •NO and superoxide anions and the impact of the thiol-disulfide system on •NO's properties. Overall, the article provides a comprehensive overview of the complex roles of •NO in health and disease, highlighting the need for further research to understand and modulate its actions for therapeutic purposes.