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The interplay involving oxidative stress and autophagy: Mechanisms, implications, and therapeutic opportunities

Noha Gouda, Assem Zhakupova, Ahmed M. Abdelaal, Firdos Ahmad, Ahmed Elkamhawy

2025Experimental and Molecular Pathology22 citationsDOIOpen Access PDF

Abstract

Reactive oxygen species (ROS) are extremely reactive molecules produced during cellular metabolism, which play important roles in signaling and immune responses. Excessive ROS accumulation results in oxidative stress and cellular damage. As a result, autophagy (a cellular recycling process) is induced to overcome oxidative stress conditions by eliminating impaired cellular components. By selectively targeting and degrading dysfunctional mitochondria and peroxisomes through mitophagy and pexophagy, respectively, cells can effectively reduce ROS accumulation. Conversely, oxidative stress can disrupt autophagy, impairing protein aggregate clearance and thereby exacerbating ROS accumulation. In this review, we discuss the complex correlation between oxidative stress and autophagy, highlighting the mechanisms of regulation and their pathological implications. Additionally, we discuss the latest advances and challenges in developing autophagy-modulating therapies.

Topics & Concepts

AutophagyMitophagyOxidative stressReactive oxygen speciesCell biologyMitochondrionPeroxisomeBiologyChemistryBiochemistryApoptosisReceptorAutophagy in Disease and TherapyCannabis and Cannabinoid ResearchCalcium signaling and nucleotide metabolism