ArticleMitochondrion2016
Metabolic flexibility of mitochondrial respiratory chain disorders predicted by computer modelling.
Article in Mitochondrion, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Statins effect on insulin resistance after a meal and exercise in hypercholesterolemic pre-diabetic individuals.Scandinavian journal of medicine & science in sports · 2022Trial
- Hypoxia rescues complex 1-associated disease caused by proteostatic defects.Nature metabolism · 2026Article
- A primary mechanism for efficacy of the ketogenic diet may be energy repletion at the tripartite synapse.Journal of neural engineering · 2025Article
- Sulfide Quinone Oxidoreductase Alleviates Acute Ulcerative Colitis by Regulating Mitochondrial Dysfunction.MedComm · 2025Article
- Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.Physiology (Bethesda, Md.) · 2024Review
- The Ubiquinone-Ubiquinol Redox Cycle and Its Clinical Consequences: An Overview.International journal of molecular sciences · 2024Review
- Aging-Related Mitochondrial Dysfunction Is Associated With Fibrosis in Benign Prostatic Hyperplasia.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Pathophysiology of Cerebellar Degeneration in Mitochondrial Disorders: Insights from theInternational journal of molecular sciences · 2023Article
- Proline Oxidation Supports Mitochondrial ATP Production When Complex I Is Inhibited.International journal of molecular sciences · 2022Article
- Inhibition of the succinyl dehydrogenase complex in acute myeloid leukemia leads to a lactate-fuelled respiratory metabolic vulnerability.Nature communications · 2022Article
- Bezafibrate Rescues Mitochondrial Encephalopathy in Mice via Induction of Daily Torpor and Hypometabolic State.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Apoptosis-Inducing Factor Deficiency Induces Tissue-Specific Alterations in Autophagy: Insights from a Preclinical Model of Mitochondrial Disease and Exercise Training Effects.Antioxidants (Basel, Switzerland) · 2022Article
- The Effects of Bilirubin and Lumirubin on Metabolic and Oxidative Stress Markers.Frontiers in pharmacology · 2021Article
- β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice.Life (Basel, Switzerland) · 2020Article
- Article
- Article
- Impaired mitochondrial complex I function as a candidate driver in the biological stress response and a concomitant stress-induced brain metabolic reprogramming in male mice.Translational psychiatry · 2020Article
- Mitochondrial peptide BRAWNIN is essential for vertebrate respiratory complex III assembly.Nature communications · 2020Article
- Article
- Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose.PloS one · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial respiratory chain dysfunction causes a variety of life-threatening diseases affecting about 1 in 4300 adults. These diseases are genetically heterogeneous, but have the same outcome; reduced activity of mitochondrial respiratory chain complexes causing decreased ATP production and potentially toxic accumulation of metabolites. Severity and tissue specificity of these effects varies between patients by unknown mechanisms and treatment options are limited. So far most research has focused on the complexes themselves, and the impact on overall cellular metabolism is largely unclear. To illustrate how computer modelling can be used to better understand the potential impact of these disorders and inspire new research directions and treatments, we simulated them using a computer model of human cardiomyocyte mitochondrial metabolism containing over 300 characterised reactions and transport steps with experimental parameters taken from the literature. Overall, simulations were consistent with patient symptoms, supporting their biological and medical significance. These simulations predicted: complex I deficiencies could be compensated using multiple pathways; complex II deficiencies had less metabolic flexibility due to impacting both the TCA cycle and the respiratory chain; and complex III and IV deficiencies caused greatest decreases in ATP production with metabolic consequences that parallel hypoxia. Our study demonstrates how results from computer models can be compared to a clinical phenotype and used as a tool for hypothesis generation for subsequent experimental testing. These simulations can enhance understanding of dysfunctional mitochondrial metabolism and suggest new avenues for research into treatment of mitochondrial disease and other areas of mitochondrial dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
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.