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Article

Antioxidant Effects of Exogenous Mitochondria: The Role of Outer Membrane Integrity

1
Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, Tokyo 184-8588, Japan
2
Department of Pharmacy, International Islamic University Chittagong, Chittagong 4318, Bangladesh
3
Department of Pharmacy, University of Chittagong, Chittagong 4331, Bangladesh
*
Author to whom correspondence should be addressed.
Antioxidants 2025, 14(8), 951; https://doi.org/10.3390/antiox14080951 (registering DOI)
Submission received: 9 June 2025 / Revised: 18 July 2025 / Accepted: 28 July 2025 / Published: 2 August 2025
(This article belongs to the Section ROS, RNS and RSS)

Abstract

The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but differing in outer membrane integrity. To evaluate their stability in extracellular conditions, we examined their behavior in serum. Both types underwent mitochondrial permeability transition to a similar extent; however, under intracellular-like conditions after serum incubation, mitochondria with intact membranes retained more polarized mitochondria. Notably, mitochondria with intact outer membranes were internalized more efficiently than those with damaged membranes. In H9c2 cells, both types of mitochondria similarly increased intracellular ATP levels 1 h after administration under all tested conditions. When co-administered with H2O2, both suppressed oxidative damage to a comparable degree, as indicated by similar H2O2-scavenging activity in solution, comparable intracellular ROS levels, and equivalent preservation of electron transport chain activity. However, at higher H2O2 concentrations, cells treated with mitochondria possessing intact outer membranes exhibited greater survival 24 h after co-administration. Furthermore, when mitochondria were added after H2O2-induced damage and their removal, intact mitochondria conferred superior cell survival compared to damaged ones. These findings suggest that while both mitochondrial types exert comparable antioxidant effects, outer membrane integrity prior to administration plays a critical role in enhancing cell survival under conditions of oxidative stress.
Keywords: mitochondrial administration; cryopreserved mitochondria; oxidative damage; ROS mitochondrial administration; cryopreserved mitochondria; oxidative damage; ROS

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MDPI and ACS Style

Ibban, S.S.; Naima, J.; Kato, R.; Kuroda, T.; Ohta, Y. Antioxidant Effects of Exogenous Mitochondria: The Role of Outer Membrane Integrity. Antioxidants 2025, 14, 951. https://doi.org/10.3390/antiox14080951

AMA Style

Ibban SS, Naima J, Kato R, Kuroda T, Ohta Y. Antioxidant Effects of Exogenous Mitochondria: The Role of Outer Membrane Integrity. Antioxidants. 2025; 14(8):951. https://doi.org/10.3390/antiox14080951

Chicago/Turabian Style

Ibban, Sadab Sipar, Jannatul Naima, Ryo Kato, Taichi Kuroda, and Yoshihiro Ohta. 2025. "Antioxidant Effects of Exogenous Mitochondria: The Role of Outer Membrane Integrity" Antioxidants 14, no. 8: 951. https://doi.org/10.3390/antiox14080951

APA Style

Ibban, S. S., Naima, J., Kato, R., Kuroda, T., & Ohta, Y. (2025). Antioxidant Effects of Exogenous Mitochondria: The Role of Outer Membrane Integrity. Antioxidants, 14(8), 951. https://doi.org/10.3390/antiox14080951

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