ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Metformin Restores Mitochondrial Function and Neurogenesis in POLG Patient-Derived Brain Organoids.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
1 citing paper in PubMed.
- Metformin Restores Mitochondrial Function and Neurogenesis in POLG Patient-Derived Brain Organoids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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Authors and funding
7 authors.
Funding
Abstract
Mitochondrial dysfunction and impaired neurogenesis are central to mitochondrial DNA polymerase (POLG)-related disorders, yet therapeutic options remain limited. Here, patient-derived induced pluripotent stem cell (iPSC)-based cortical organoids are used to model POLG-associated neurodegeneration and assess the therapeutic potential of metformin. Single-cell RNA-seq reveals distinct vulnerabilities in dopaminergic, glutamatergic, and GABAergic neuronal subtypes, with dopaminergic neurons exhibiting the most severe loss and mitochondrial transcriptomic deficits. Metformin treatment (250 µm, 2 months) significantly restores neuronal identity, subtype-specific gene expression, and mitochondrial function. Functional assays demonstrate improved mitochondrial membrane potential (TMRE), increased mitochondrial mass (MTG, MTDR), and reduced oxidative stress (MitoSOX, BAX/cleaved caspase 3). Notably, mitochondrial DNA (mtDNA) copy number and the expression of mitochondrial replisome proteins (POLG, POLG2) are upregulated, indicating enhanced mitochondrial genome maintenance. Calcium measurement confirms improved neuronal excitability. Untargeted metabolomics further reveals metformin-induced metabolic reprogramming, including enrichment of the tricarboxylic acid (TCA) cycle, amino acid metabolism, and redox-related pathways. Together, these findings demonstrate that metformin enhances mitochondrial integrity and neural function across multiple neuronal subtypes and offer mechanistic insights into its potential as a treatment for POLG-related disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.