Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression

Sep 22, 2026

Normal cells preferentially use mitochondrial oxidative phosphorylation for energy under aerobic conditions, yet electron leakage during respiration generates superoxide anions (·O2−) that continuously challenge redox balance. Superoxide dismutase 2 (SOD2), a mitochondria-matrix antioxidant enzyme also known as MnSOD, converts ·O2− to hydrogen peroxide (H2O2) to prevent mitochondrial oxidative damage. This review synthesizes findings linking SOD2-dependent regulation to cancer proliferation, cell cycle progression, invasion, metastasis, metabolic reprogramming, apoptosis, autophagy, angiogenesis, and immune responses. Targeting SOD2-mediated vulnerabilities may support novel anticancer strategies.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages30

Reading Time1 h 16 min

AccessFree to download

Abstract

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Author Manuscript Author Manuscript Author Manuscript Author Manuscript | | HHS Public Access
Author manuscript
Free Radic Res. Author manuscript; available in PMC 2026 May 02. | | --- | --- | Published in final edited form as: Free Radic Res. 2026 February ; 60(2): 183–200. doi:10.1080/10715762.2026.2643692 . Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression Md Rafikul Islama,b, Rashedul Alamc, Farhadul Islamd, Preeti Nagara,b, Mohammad Alinoor Rahmana,b a Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA; bWinthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR, USA; c Department of Biotechnology, Harrisburg University of Science and Technology, Harrisburg, PA, USA; d Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh Abstract Normal cells preferably utilize mitochondrial oxidative phosphorylation as the primary source of energy in aerobic conditions. However, superoxide anions (·O2 − ) are produced as a by-product due to leakage of the electron from the electron transport chain during oxidative phosphorylation, and cells are continuously exposed to elevated levels of superoxide. Superoxide dismutase 2 (SOD2, also called manganese superoxide dismutase or MnSOD) is a mitochondria-matrixlocalized antioxidant enzyme that prevents oxidative damage to mitochondria by converting ·O2 − to hydrogen peroxide (H 2O2). Previous studies reported the roles of SOD2 in regulating cellular metabolism and the connection of variable SOD2 levels and activity with diverse types and stages of cancer. In this review, we systematically summarize recent findings on the roles of SOD2 in cancer cell proliferation, cell cycle progression, invasion, metastasis, metabolic reprogramming, apoptosis, autophagy, angiogenesis, and immune response. Understanding the regulatory factors and signaling pathways of cancer development and progression mediated by SOD2 could help to target critical cellular vulnerabilities to develop novel therapeutic strategies against cancer. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. ✉ CONTACT Md Rafikul [Islam islammdr@uams.edu](Islam islammdr@uams.edu); Mohammad Alinoor Rahman marahman@uams.edu Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. Authors contributions CRediT: Md Rafikul Islam: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing; Rashedul Alam: Writing – original draft, Writing – review & editing; Farhadul Islam: Supervision, Validation, Writing – review & editing; Preeti Nagar: Writing – original draft, Writing – review & editing; Mohammad Alinoor Rahman: Conceptualization, Investigation, Resources, Software, Supervision, Validation, Writing – review & editing. Disclosure statement No potential conflict of interest was reported by the authors. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Islam et al. Page 2 Keywords Antioxidant enzyme; cancer; cell proliferation; metastasis; metabolism Introduction Mitochondria are the central hubs to produce cellular energy and reactive oxygen specie

FAQs

What is SOD2 and what does it do in mitochondria?

SOD2 (MnSOD) is a mitochondria-matrix-localized antioxidant enzyme that converts superoxide radicals (·O2−) into hydrogen peroxide (H2O2), helping prevent oxidative damage.

Why do normal cells produce superoxide during oxidative phosphorylation?

During respiration, electron leakage from the mitochondrial electron transport chain can generate superoxide radicals, exposing cells to elevated reactive oxygen species under normal conditions.

How does SOD2 relate to cancer development and progression?

The review summarizes evidence that variable SOD2 levels and activity influence multiple cancer hallmarks, including proliferation, cell cycle progression, invasion, metastasis, metabolic reprogramming, apoptosis, autophagy, angiogenesis, and immune response.

Sep 22, 2026

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