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FoxO3 and oxidative stress: a multifaceted role in cellular adaptation

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Abstract

Oxidative stress is a major cause of morbidity and mortality in human health and disease. In this review, we focus on the Forkhead Box (Fox) subclass O3 (FoxO3), an extensively studied transcription factor that plays a pleiotropic role in a wide range of physiological and pathological processes by regulating multiple gene regulatory networks involved in the modulation of numerous aspects of cellular metabolism, including fuel metabolism, cell death, and stress resistance. This review will also focus on regulatory mechanisms of FoxO3 expression and activity, such as crucial post-translational modifications and non-coding RNAs. Moreover, this work discusses and evidences some pathways to how this transcription factor and reactive oxygen species regulate each other, which may lead to the pathogenesis of various types of diseases. Therefore, in addition to being a promising therapeutic target, the FoxO3-regulated signaling pathways can also be used as reliable diagnostic and prognostic biomarkers and indicators for drug responsiveness.

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Funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant number 406700/2021–4), and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (CAPES)–Finance Code 001.

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  1. Department of Biology, Universidade Estadual Paulista (UNESP), São Paulo, Brazil

    Victoria Simões Bernardo, Flaviene Felix Torres & Danilo Grünig Humberto da Silva

  2. Campus de Três Lagoas, Universidade Federal de Mato Grosso Do Sul (CPTL/UFMS), Avenida Ranulpho Marques Leal, 3484, Três Lagoas, Mato Grosso Do Sul, Distrito Industrial–Post code 79613-000, Brazil

    Danilo Grünig Humberto da Silva

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VSB and FFT conceived, reviewed the literature, and wrote the manuscript. DGHS reviewed and edited the manuscript. All authors were involved in reading and approving the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Bernardo, V.S., Torres, F.F. & da Silva, D.G.H. FoxO3 and oxidative stress: a multifaceted role in cellular adaptation. J Mol Med 101, 83–99 (2023). https://doi.org/10.1007/s00109-022-02281-5

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