ArticleExperimental neurology2020
Mapping mitochondrial respiratory chain deficiencies by respirometry: Beyond the Mito Stress Test.
Article in Experimental neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- A Viscous DES-AAV-Foxo1 Delivery System With High Transfection Efficiency for the Treatment of Corneal Endothelial Dysfunction by Restoring Mitochondria-ER Contacts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ER Proteotoxic Stress Drives Mitochondrial Dysfunction in Heat-Stressed Intestinal Epithelial Cells.Cells · 2026Article
- Mitochondrial bioenergetics and intracellular calcium concentration in primary myotubes from mouse models of malignant hyperthermia.British journal of anaesthesia · 2026Article
- CRABS-ROC, A respirometry protocol for overcoming substrate limitations, reveals excess brain mitochondrial Complex I capacity.Free radical biology & medicine · 2025Article
- Alcohol and Metabolic Stress Synergize to Dysregulate Mitochondrial Health and Lipid Metabolism; Evidence from a Hepatocyte Spheroid Model.Function (Oxford, England) · 2025Article
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- A Comparison ofInorganica chimica acta · 2024Article
- An efficient and high-throughput method for the evaluation of mitochondrial dysfunction in frozen brain samples after traumatic brain injury.Frontiers in molecular biosciences · 2024Article
- BZD9L1 Differentially Regulates Sirtuins in Liver-Derived Cells by Inducing Reactive Oxygen Species.Biomedicines · 2023Article
- Fundamental Neurochemistry Review: Microglial immunometabolism in traumatic brain injury.Journal of neurochemistry · 2023Review
- Inhibition of monoamine oxidase-a increases respiration in isolated mouse cortical mitochondria.Experimental neurology · 2023Article
- Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson's Disease Model by Alleviating Mitochondrial Dysfunction.International journal of molecular sciences · 2023Article
- Targeting mitochondrial metabolism for metastatic cancer therapy.Molecular carcinogenesis · 2022Review
- Recent Approaches to Determine Static and Dynamic Redox State-Related Parameters.Antioxidants (Basel, Switzerland) · 2022Review
- From OCR and ECAR to energy: Perspectives on the design and interpretation of bioenergetics studies.The Journal of biological chemistry · 2021Review
- ALS/FTD mutations in UBQLN2 are linked to mitochondrial dysfunction through loss-of-function in mitochondrial protein import.Human molecular genetics · 2021Article
- Considerations for using isolated cell systems to understand cardiac metabolism and biology.Journal of molecular and cellular cardiology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cell-based respirometers, such as the Seahorse Extracellular Flux Analyzer, are valuable tools to assess the functionality of mitochondria within adherent neurons, as well as other cell types. The Mito Stress Test is the most frequently employed protocol of drug additions to evaluate mitochondrial bioenergetic function. Sequential exposure of cells to an ATP synthase inhibitor such as oligomycin and an uncoupler such as FCCP cause changes in oxygen consumption rate that allow estimation of the cellular efficiency and capacity for mitochondrial ATP synthesis. While a useful first step in assessing whether an experimental treatment or genetic manipulation affects mitochondrial energetics, the Mito Stress Test does not identify specific sites of altered respiratory chain function. This article discusses limitations of the Mito Stress Test, proposes a refined protocol for comparing cell populations that requires independent drug titrations at multiple cell densities, and describes a stepwise series of respirometry-based assays that "map" locations of electron transport deficiency. These include strategies to test for cytochrome c release, to probe the functionality of specific electron transport chain complexes within intact or permeabilized cells, and to measure NADH oxidation by the linked activity of Complexes I, III, and IV. To illustrate utility, we show that although UK5099 and ABT-737 each decrease the spare respiratory capacity of cortical neurons, the stepwise assays reveal different underlying mechanisms consistent with their established drug targets: deficient Complex I substrate supply induced by the mitochondrial pyruvate carrier inhibitor UK5099 and cytochrome c release induced by the anti-apoptotic BCL-2 family protein inhibitor ABT-737.
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