Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy
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Issued Date
2025-01-01
Resource Type
eISSN
22115463
Scopus ID
2-s2.0-105022830044
Pubmed ID
41277319
Journal Title
FEBS Open Bio
Rights Holder(s)
SCOPUS
Bibliographic Citation
FEBS Open Bio (2025)
Suggested Citation
Panusatid C., Soiyangsuk R., Tanadjindarat M., Peerapittayamongkol C. Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy. FEBS Open Bio (2025). doi:10.1002/2211-5463.70165 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113335
Title
Metformin promotes mitochondrial integrity through AMPK-signaling in Leber's hereditary optic neuropathy
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Leber's hereditary optic neuropathy (LHON) is a maternally inherited disorder caused by mitochondrial DNA mutations in complex I of the respiratory chain, leading to impaired ATP production, mitochondrial fragmentation, and oxidative stress that contribute to vision loss. This study investigated the potential repurposing of metformin, a widely used antidiabetic drug, in fibroblasts from LHON patients carrying the m.11778G>A mutation. Fibroblasts from LHON patients and healthy individuals were treated with metformin, and mitochondrial function was assessed using high-content imaging, biochemical assays, immunoblotting, immunofluorescence, and Seahorse analysis. Metformin reduced mitochondrial fragmentation, increased network length, stabilized mitochondrial membrane potential, enhanced ATP production, and lowered ROS accumulation under oxidative stress. Metformin significantly increased mitophagy and autophagic flux, as shown by LC3B puncta quantification with and without chloroquine, and activated AMPK signaling through increased AMPKα1/2 phosphorylation and AMPKβ1 Ser182 phosphorylation. In addition, metformin promoted PGC-1α nuclear translocation, indicating stimulation of mitochondrial biogenesis, while maintaining mtDNA copy number and supporting oxidative phosphorylation. These findings suggest that metformin, at clinically relevant concentrations, enhances mitochondrial health and function in LHON fibroblasts, supporting its potential as an affordable and safe therapeutic option to mitigate vision loss in LHON.