Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Exploring the Gut-Mitochondrial Axis: the p66Shc Adapter Protein and Its Implications for Metabolic Disorders

Version 1 : Received: 19 February 2024 / Approved: 20 February 2024 / Online: 20 February 2024 (07:10:10 CET)

A peer-reviewed article of this Preprint also exists.

da C. Pinaffi-Langley, A.C.; Melia, E.; Hays, F.A. Exploring the Gut–Mitochondrial Axis: p66Shc Adapter Protein and Its Implications for Metabolic Disorders. Int. J. Mol. Sci. 2024, 25, 3656. da C. Pinaffi-Langley, A.C.; Melia, E.; Hays, F.A. Exploring the Gut–Mitochondrial Axis: p66Shc Adapter Protein and Its Implications for Metabolic Disorders. Int. J. Mol. Sci. 2024, 25, 3656.

Abstract

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 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.

Keywords

p66Shc; adaptor protein; oxidative stress; gut microbiota; inflammation; mitochondrial dysfunction

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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