Oxidative Stress in the Regulation of Autosis-Related Proteins

Guerra-Andrés, María; Martínez-Rojo, Inés; Piedra-Macías, Alejandra; Lavado-Fernández, Elena; García-Macia, Marina; F. Fernández, Álvaro

doi:10.3390/antiox14080958

Open AccessReview

Oxidative Stress in the Regulation of Autosis-Related Proteins

by

María Guerra-Andrés

^1,2,

Inés Martínez-Rojo

³,

Alejandra Piedra-Macías

^1,2

,

Elena Lavado-Fernández

^3,4,

Marina García-Macia

^3,4,*

and

Álvaro F. Fernández

^1,2,5,*

¹

Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, 33006 Oviedo, Spain

²

Instituto Universitario de Oncología del Principado de Asturias (IUOPA), 33006 Oviedo, Spain

³

Instituto de Biología Funcional y Genómica (IBFG), Universidad de Salamanca/CSIC, 37007 Salamanca, Spain

⁴

Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, 37007 Salamanca, Spain

⁵

Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain

^*

Authors to whom correspondence should be addressed.

Antioxidants 2025, 14(8), 958; https://doi.org/10.3390/antiox14080958

Submission received: 10 June 2025 / Revised: 23 July 2025 / Accepted: 1 August 2025 / Published: 4 August 2025

(This article belongs to the Special Issue Crosstalk between Autophagy and Oxidative Stress)

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Abstract

Physiological levels of reactive oxygen species (ROS) play a crucial role as intracellular signaling molecules, helping to maintain cellular homeostasis. However, when ROS accumulate excessively, they become toxic to cells, leading to damage to lipids, proteins, and DNA. This oxidative stress can impair cellular function and lead to various forms of cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis. Despite their significance, the role of ROS in autosis (an autophagy-dependent form of cell death) remains largely unexplored. In this review, we gather current knowledge on autotic cell death and summarize how oxidative stress influences the activity of Beclin-1 and the Na⁺,K⁺-ATPase pump, both of which are critical effectors of this pathway. Finally, we discuss the theoretical potential for ROS to modulate this type of cell death, proposing a possible dual role for these species in autosis regulation through effectors such as HIF-1α, TFEB, or the FOXO family, and highlighting the need to experimentally address cellular redox status when working on autotic cell death.

Keywords: autosis; ROS; oxidative stress; Beclin-1; Na⁺,K⁺-ATPase; autophagy

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MDPI and ACS Style

Guerra-Andrés, M.; Martínez-Rojo, I.; Piedra-Macías, A.; Lavado-Fernández, E.; García-Macia, M.; F. Fernández, Á. Oxidative Stress in the Regulation of Autosis-Related Proteins. Antioxidants 2025, 14, 958. https://doi.org/10.3390/antiox14080958

AMA Style

Guerra-Andrés M, Martínez-Rojo I, Piedra-Macías A, Lavado-Fernández E, García-Macia M, F. Fernández Á. Oxidative Stress in the Regulation of Autosis-Related Proteins. Antioxidants. 2025; 14(8):958. https://doi.org/10.3390/antiox14080958

Chicago/Turabian Style

Guerra-Andrés, María, Inés Martínez-Rojo, Alejandra Piedra-Macías, Elena Lavado-Fernández, Marina García-Macia, and Álvaro F. Fernández. 2025. "Oxidative Stress in the Regulation of Autosis-Related Proteins" Antioxidants 14, no. 8: 958. https://doi.org/10.3390/antiox14080958

APA Style

Guerra-Andrés, M., Martínez-Rojo, I., Piedra-Macías, A., Lavado-Fernández, E., García-Macia, M., & F. Fernández, Á. (2025). Oxidative Stress in the Regulation of Autosis-Related Proteins. Antioxidants, 14(8), 958. https://doi.org/10.3390/antiox14080958

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Oxidative Stress in the Regulation of Autosis-Related Proteins

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