Department of Nutritional Sciences, College of Allied Health, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA.
Stephenson Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK 73117, USA.
Int J Mol Sci. 2024 Mar 25;25(7):3656. doi: 10.3390/ijms25073656.
This review investigates the multifaceted role of the p66Shc adaptor protein and the gut microbiota in regulating mitochondrial function and oxidative stress, and their collective impact on the pathogenesis of chronic diseases. The study delves into the molecular mechanisms by which p66Shc influences cellular stress responses through Rac1 activation, Forkhead-type transcription factors inactivation, and mitochondria-mediated apoptosis, alongside modulatory effects of gut microbiota-derived metabolites and endotoxins. Employing an integrative approach, the review synthesizes findings from a broad array of studies, including molecular biology techniques and analyses of microbial metabolites' impacts on host cellular pathways. The results underscore a complex interplay between microbial metabolites, p66Shc activation, and mitochondrial dysfunction, highlighting the significance of the gut microbiome in influencing disease outcomes through oxidative stress pathways. Conclusively, the review posits that targeting the gut microbiota-p66Shc-mitochondrial axis could offer novel therapeutic strategies for mitigating the development and progression of metabolic diseases. This underscores the potential of dietary interventions and microbiota modulation in managing oxidative stress and inflammation, pivotal factors in chronic disease etiology.
本综述探讨了 p66Shc 衔接蛋白和肠道微生物群在调节线粒体功能和氧化应激方面的多方面作用，以及它们对慢性疾病发病机制的共同影响。该研究深入探讨了 p66Shc 通过 Rac1 激活、叉头型转录因子失活和线粒体介导的细胞凋亡影响细胞应激反应的分子机制，以及肠道微生物群衍生代谢物和内毒素的调节作用。该综述采用综合方法，综合了来自广泛研究的发现，包括分子生物学技术和分析微生物代谢物对宿主细胞途径的影响。研究结果强调了微生物代谢物、p66Shc 激活和线粒体功能障碍之间的复杂相互作用，突出了肠道微生物组通过氧化应激途径影响疾病结果的重要性。总之，该综述认为靶向肠道微生物群-p66Shc-线粒体轴可能为减轻代谢性疾病的发展和进展提供新的治疗策略。这凸显了饮食干预和微生物群调节在管理氧化应激和炎症方面的潜力，氧化应激和炎症是慢性疾病病因的关键因素。
