ArticleScience advances2025
Metabolic rewiring caused by mitochondrial dysfunction promotes mTORC1-dependent skeletal aging.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed.
- Vertebral BMSC-EVs under estrogen deficiency drive senescence-related mitochondrial dysfunction in endplate chondrocytes via MRPL1 mRNA delivery.Experimental & molecular medicine · 2026Article
- Leveraging Pretrained Neural Network Models for the Classification of Tumor Cells Analyzed by Label-Free Phase Holotomographic Microscopy.Computational and structural biotechnology journal · 2026Article
- Piezo1-Fstl1 Axis in Fracture Healing: Modulation of the Chondrocyte Inflammation-ROS-Mitochondrial Damage Cascade and Application of Smart Delivery System.International journal of biological sciences · 2026Article
- The microbiome-gerogene axis: a new frontier in precision geromedicine.Frontiers in aging · 2026Review
- Multi-target synergistic anti-aging: QG extends Caenorhabditis elegans lifespan through DAF-16/FOXO pathways, mitochondrial homeostasis and metabolic reprogramming.Biogerontology · 2025Article
- Electroacupuncture ameliorates cognitive dysfunction in T2DM rats by modulating astrocytic polarization and aberrant energy metabolism in the hippocampus via the Wnt/β-catenin pathway.Diabetology & metabolic syndrome · 2025Article
- Tendinopathy: The Interplay between Mechanical Stress, Inflammation, and Vascularity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decline of mitochondrial respiratory chain (mtRC) capacity is a hallmark of mitochondrial diseases. Patients with mtRC dysfunction often present reduced skeletal growth as a sign of premature cartilage degeneration and aging, but how metabolic adaptations contribute to this phenotype is poorly understood. Here we show that, in mice with impaired mtRC in cartilage, reductive/reverse TCA cycle segments are activated to produce metabolite-derived amino acids and stimulate biosynthesis processes by mechanistic target of rapamycin complex 1 (mTORC1) activation during a period of massive skeletal growth and biomass production. However, chronic hyperactivation of mTORC1 suppresses autophagy-mediated organelle recycling and disturbs extracellular matrix secretion to trigger chondrocytes death, which is ameliorated by targeting the reductive metabolism. These findings explain how a primarily beneficial metabolic adaptation response required to counterbalance the loss of mtRC function, eventually translates into profound cell death and cartilage tissue degeneration. The knowledge of these dysregulated key nutrient signaling pathways can be used to target skeletal aging in mitochondrial disease.
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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 OpenQuestion graph.