Coordinated mitochondrial quality control underlies oxidative stress resilience in MUSE stem cells.
6 affiliations
- 1Department of Life Sciences, Health and Health Professions, Link Campus University, Rome, Italy.
- 2Department of Experimental Medicine, Luigi Vanvitelli Campania University, Naples, Italy.
- 3Department of Biotechnology, University of Samarra, Samarra, Iraq.
- 4Department of Medical Laboratory Sciences, Bahir Dar University, Bahir Dar, Ethiopia.
- 5Saint Camillus International University of Health and Medical Sciences, UNICAMILLUS, Rome, Italy.
- 6Genome and Stem Cell Center (GENKÖK), Erciyes University, Kayseri, Turkey.
Abstract
Background
Reactive oxygen species (ROS) regulate stem-cell function, but sustained exposure causes oxidative damage, mitochondrial dysfunction and exhaustion. Multilineage-differentiating Stress-Enduring (MUSE) cells, a rare SSEA-3⁺ MSC subset, tolerate ROS-rich environments, although the mechanisms remain unclear.Methods
We compared MUSE, Non-MUSE (SSEA-3⁻) and MSCs after H₂O₂ exposure, assessing ROS clearance, mtDNA integrity, 8-oxo-dG, antioxidant and BER responses, mitochondrial morphology/function, mitophagy and biogenesis, with focus on the PGC-1α/NRF2 axis. Three independent biological replicates were analyzed by imaging, qPCR, flow cytometry and biochemical assays.Results
MUSE cells showed greater resistance to oxidative stress than MSCs and Non-MUSE cells. After H₂O₂, they displayed lower ROS accumulation (~15-25%), preserved mtDNA integrity, reduced 8-oxo-dG, rapid induction of antioxidant and BER-related genes, and maintenance of mitochondrial morphology, membrane potential and respiratory activity. MUSE cells also showed enhanced mitophagy, with >2-fold increased LAMP1-MitoTracker colocalization and induction of PINK1/phospho-Ub-S65, together with increased biogenesis, including ~45% higher COX-I/SDHA ratio, TFAM induction and PGC-1α activation at 48 h.Conclusion
MUSE cells coordinate antioxidant defense, DNA repair, mitophagy and biogenesis through a remove-and-replace program that preserves mitochondrial function during oxidative stress.
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BibTeX
@article{aprile2026coordinated,
title = {{Coordinated mitochondrial quality control underlies oxidative stress resilience in MUSE stem cells.}},
author = {Domenico Aprile and Sura Hilal Ahmed Al-Sammarraie and Alessia Ambrosino and Mohd Shahzaib and Yesuf Siraj and Afshin Samiminemati and Nicola Alessio and Gianfranco Peluso and Giovanni Di Bernardo and Umberto Galderisi},
journal = {Redox report : communications in free radical research},
year = {2026},
month = oct,
doi = {10.1080/13510002.2026.2698189},
url = {https://europepmc.org/article/MED/42852617},
note = {CC BY},
}
RIS
TY - JOUR
TI - Coordinated mitochondrial quality control underlies oxidative stress resilience in MUSE stem cells.
AU - Domenico Aprile
AU - Sura Hilal Ahmed Al-Sammarraie
AU - Alessia Ambrosino
AU - Mohd Shahzaib
AU - Yesuf Siraj
AU - Afshin Samiminemati
AU - Nicola Alessio
AU - Gianfranco Peluso
AU - Giovanni Di Bernardo
AU - Umberto Galderisi
PY - 2026
DA - 2026/10/09
JO - Redox report : communications in free radical research
DO - 10.1080/13510002.2026.2698189
UR - https://europepmc.org/article/MED/42852617
AB - Background Reactive oxygen species (ROS) regulate stem-cell function, but sustained exposure causes oxidative damage, mitochondrial dysfunction and exhaustion. Multilineage-differentiating Stress-Enduring (MUSE) cells, a rare SSEA-3⁺ MSC subset, tolerate ROS-rich environments, although the mechanisms remain unclear.Methods We compared MUSE, Non-MUSE (SSEA-3⁻) and MSCs after H₂O₂ exposure, assessing ROS clearance, mtDNA integrity, 8-oxo-dG, antioxidant and BER responses, mitochondrial morphology/function, mitophagy and biogenesis, with focus on the PGC-1α/NRF2 axis. Three independent biological replicates were analyzed by imaging, qPCR, flow cytometry and biochemical assays.Results MUSE cells showed greater resistance to oxidative stress than MSCs and Non-MUSE cells. After H₂O₂, they displayed lower ROS accumulation (~15-25%), preserved mtDNA integrity, reduced 8-oxo-dG, rapid induction of antioxidant and BER-related genes, and maintenance of mitochondrial morphology, membrane potential and respiratory activity. MUSE cells also showed enhanced mitophagy, with >2-fold increased LAMP1-MitoTracker colocalization and induction of PINK1/phospho-Ub-S65, together with increased biogenesis, including ~45% higher COX-I/SDHA ratio, TFAM induction and PGC-1α activation at 48 h.Conclusion MUSE cells coordinate antioxidant defense, DNA repair, mitophagy and biogenesis through a remove-and-replace program that preserves mitochondrial function during oxidative stress.
SN - 1351-0002
SN - 1743-2928
ER -