Mitochondrial dysfunction and endoplasmic reticulum stress (ERS) are global processes that are interrelated and regulated by several stress factors. Nitric oxide (NO) is a multifunctional biomolecule with many varieties of physiological and pathological functions, such as the regulation of cytochrome c inhibition and activation of the immune response, ERS and DNA damage; these actions are dose-dependent. It has been reported that in embryonic stem cells, NO has a dual role, controlling differentiation, survival and pluripotency, but the molecular mechanisms by which it modulates these functions are not yet known. Low levels of NO maintain pluripotency and induce mitochondrial biogenesis. It is well established that NO disrupts the mitochondrial respiratory chain and causes changes in mitochondrial Ca²⁺ flux that induce ERS. Thus, at high concentrations, NO becomes a potential differentiation agent due to the relationship between ERS and the unfolded protein response in many differentiated cell lines. Nevertheless, many studies have demonstrated the need for physiological levels of NO for a proper ERS response. In this review, we stress the importance of the relationships between NO levels, ERS and mitochondrial dysfunction that control stem cell fate as a new approach to possible cell therapy strategies.

中文翻译：

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多能干细胞中一氧化氮对线粒体功能和内质网应激的调节。

线粒体功能障碍和内质网应激（ERS）是相互关联并受多种应激因素调控的整体过程。一氧化氮（NO）是一种具有多种生理和病理功能的多功能生物分子，例如调节细胞色素c的抑制作用和激活免疫反应，ERS和DNA损伤；这些作用是剂量依赖性的。据报道，在胚胎干细胞中，NO具有双重作用，可控制分化，存活和多能性，但尚不清楚调节这些功能的分子机制。低水平的NO维持多能性并诱导线粒体生物发生。众所周知，NO会破坏线粒体呼吸链并导致线粒体Ca ²⁺发生变化导致ERS的通量。因此，在高浓度下，由于ERS与许多分化细胞系中未折叠的蛋白质反应之间的关系，NO成为潜在的分化剂。然而，许多研究表明需要生理水平的NO才能获得正确的ERS反应。在这篇综述中，我们强调控制干细胞命运的NO水平，ERS和线粒体功能障碍之间关系的重要性，以此作为可能的细胞治疗策略的新方法。