ArticleCommunications biology2023
OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases.
Article in Communications biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06080568 (Energy Balance and Mitochondrial Function in Human Genetic Models of Mitochondrial Stress-mediated Obesity Resistance), which is not on this map. Cited by 96 papers.
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.
Energy Balance and Mitochondrial Function in Human Genetic Models of Mitochondrial Stress-mediated Obesity Resistance
Who cites it
96 citing papers in PubMed.
- Review
- Concept of organ dysfunction revealed by shift in thinking from V = IR to W = VI.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Energy constraint on human health.Trends in endocrinology and metabolism: TEM · 2026Review
- Polyunsaturated fatty acid sequestration protects against mitochondrial dysfunction-induced ferroptosis.EMBO reports · 2026Article
- The Energetic Cost of Adrenergic Signaling in Primary Human Fibroblasts.bioRxiv : the preprint server for biology · 2026Article
- Chlorogenic acid attenuates skin senescence and UVR-induced photoaging via the modulation of mitochondrial function.Journal of translational medicine · 2026Article
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- Natural Small Molecules Targeting Oxidative Stress and Redox Homeostasis in Aging: Mechanisms and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2026Review
- Therapeutic Impact of Mitochondrial Transplants for Cardiovascular Diseases.International journal of molecular sciences · 2026Review
- Characterization of aMolecular genetics and metabolism reports · 2026Article
- Perfluorooctane sulfonic acid (PFOS) perturbs skeletal muscle oxidative phosphorylation by a different mechanism than liver.Chemosphere · 2026Article
- Single-cell and pseudobulk analyses reveal hidden mitochondrial expression imbalance in gastric cancer.Frontiers in genetics · 2026Article
- Adaptive mechanisms in pancreatic islets counteract mitochondrial dysfunction in Barth syndrome.Diabetologia · 2026Article
- Key Experimental Therapeutics and Knowledge Gaps in Metabolic Dysfunction-Associated Steatohepatitis (MASH).Drug design, development and therapy · 2026Review
- Functional characterization of a human epilepsy-associated gene network reveals metabolic regulation as a critical factor underlying seizure susceptibilities.Disease models & mechanisms · 2026Article
- Engineering Aging: Approaches to Model and Deconstruct Biological Complexity.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- MECP2 Duplication Uncouples Mitochondrial and Purine Metabolism During neuronal maturation.bioRxiv : the preprint server for biology · 2025Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors.
Funding
Abstract
Patients with primary mitochondrial oxidative phosphorylation (OxPhos) defects present with fatigue and multi-system disorders, are often lean, and die prematurely, but the mechanistic basis for this clinical picture remains unclear. By integrating data from 17 cohorts of patients with mitochondrial diseases (n = 690) we find evidence that these disorders increase resting energy expenditure, a state termed hypermetabolism. We examine this phenomenon longitudinally in patient-derived fibroblasts from multiple donors. Genetically or pharmacologically disrupting OxPhos approximately doubles cellular energy expenditure. This cell-autonomous state of hypermetabolism occurs despite near-normal OxPhos coupling efficiency, excluding uncoupling as a general mechanism. Instead, hypermetabolism is associated with mitochondrial DNA instability, activation of the integrated stress response (ISR), and increased extracellular secretion of age-related cytokines and metabokines including GDF15. In parallel, OxPhos defects accelerate telomere erosion and epigenetic aging per cell division, consistent with evidence that excess energy expenditure accelerates biological aging. To explore potential mechanisms for these effects, we generate a longitudinal RNASeq and DNA methylation resource dataset, which reveals conserved, energetically demanding, genome-wide recalibrations. Taken together, these findings highlight the need to understand how OxPhos defects influence the energetic cost of living, and the link between hypermetabolism and aging in cells and patients with mitochondrial diseases.
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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.