ArticleAutophagy2025
Inhibition of the PI3K-AKT-MTORC1 axis reduces the burden of the m.3243A>G mtDNA mutation by promoting mitophagy and improving mitochondrial function.
Article in Autophagy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- A Multidimensional Engineering Strategy Reprograms Microglia via Targeted and Sustained-Release Extracellular Vesicles for Spinal Cord Injury Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Targeting lysosomal pH restores mitochondrial quality control in GBA1-mutant Parkinson's disease.Translational neurodegeneration · 2026Article
- Emerging therapeutic strategies for mitochondrial DNA-related diseases.Cell reports. Medicine · 2026Review
- Article
- Protein Arginine Methyltransferases in γ-Globin Regulation and Sickle Cell Disease: Emerging Connections to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2026Review
- Rescuing Mitochondrial Dysfunction in Macrophages Prevents Osteonecrosis of the Jaw in Anti-Resorptive Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- STOML2 Alleviates Osteoarthritis by Regulating Mitochondrial Energy Metabolism and Oxidative Stress.Genetics research · 2026Article
- Identifying Shared Key Genes and Cellular Characteristics Between Chronic Periodontitis and Aging Using Integrative Single-Cell and Mendelian Randomization Analyses.BioMed research international · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- When Mitochondria Falter, the Barrier Fails: Mechanisms of Inner Blood-Retinal Barrier (iBRB) Injury and Opportunities for Mitochondria-Targeted Repair.International journal of molecular sciences · 2025Review
- Targeting of the PI3 K/AKT/GSK3β Pathway in Parkinson's Disease: A Therapeutic Blueprint.Molecular neurobiology · 2025Review
- Modulation of mTOR Within Retinal Pigment Epithelium Affects Cell Viability and Mitochondrial Pathology.International journal of molecular sciences · 2025Article
- Role of mitochondria in physiological activities, diseases, and therapy.Molecular biomedicine · 2025Review
- Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies.MedComm · 2025Review
- Metabolic remodeling in hiPSC-derived myofibers carrying the m.3243A>G mutation.Stem cell reports · 2025Article
- Harnessing exercise to combat chronic diseases: the role of Drp1-Mediated mitochondrial fission.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial DNA (mtDNA) encodes genes essential for oxidative phosphorylation. The m.3243A>G mutation causes severe disease, including myopathy, lactic acidosis and stroke-like episodes (MELAS) and is the most common pathogenic mtDNA mutation in humans. We have previously shown that the mutation is associated with constitutive activation of the PI3K-AKT-MTORC1 axis. Inhibition of this pathway in patient fibroblasts reduced the mutant load, rescued mitochondrial bioenergetic function and reduced glucose dependence. We have now investigated the mechanisms that select against the mutant mtDNA under these conditions. Basal macroautophagy/autophagy and lysosomal degradation of mitochondria were suppressed in the mutant cells. Pharmacological inhibition of any step of the PI3K-AKT-MTORC1 pathway activated mitophagy and progressively reduced m.3243A>G mutant load over weeks. Inhibition of autophagy with bafilomycin A
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