Mitochondrial Dysfunction Assessed Quantitatively in Real Time by Measuring the Extracellular Flux of Oxygen and Protons

Ferrick, David A.; Wan, Min; Swift, Amy L.; Neilson, Andy

doi:10.1002/9780470372531.ch14

Cited by 3 publications

(2 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Seahorse Analyzer was programmed to sequentially add oligomycin (ATP synthase inhibitor), FCCP (protonophore uncoupling oxygen consumption from ATP production), and a combination of antimycin A (complex III inhibitor) and rotenone (complex I inhibitor) according to the instructions of the Seahorse XF Cell Mito Stress Test. Basal mitochondrial respiration, ATP-linked respiration, maximal respiratory capacity, and reserve capacity were calculated as described previously (38,39). Specifically, basal OCR and ATP-linked OCR were derived by subtracting non-mitochondrial respiration and the oligomycin rate from baseline cellular OCR, respectively.…”

Section: Manassantin Inhibits Complex I and Bioenergetic Activitymentioning

confidence: 99%

The lignan manassantin is a potent and specific inhibitor of mitochondrial complex I and bioenergetic activity in mammals

Min

Oh³

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

Dineolignans manassantin A and B from the plant are used in traditional medicine to manage a wide range of ailments such as edema, jaundice, and gonorrhea. Cell-based studies have identified several molecular target candidates of manassantin including NF-κB, MAPK, STAT3, and hypoxia-inducible factor 1α (HIF-1α). It is unclear whether or how these structurally diverse proteins or pathways mediate any of the medical benefits of manassantin Moreover, it has recently been reported that manassantin causes developmental arrest in zebrafish by inhibiting the mitochondrial complex I, but it is unknown whether manassantin inhibits mitochondrial respiration in intact mammalian cells and live animals. Here, we present direct evidence that manassantin potently and specifically inhibits the mitochondrial complex I and bioenergetic activity in mammalian systems. Manassantin had no effect on complex II- or complex IV-mediated respiration. Of note, it decreased NADH-ubiquinone reductase activity but not the activity of NADH-ferricyanide reductase. Treatment with manassantin reduced cellular ATP levels and concomitantly stimulated AMP-activated protein kinase and As an adaptive response to manassantin-induced bioenergetic deficiency, mammalian cells up-regulated aerobic glycolysis, a process mediated by AMP-activated protein kinase (AMPK) independently of HIF-1α. Together these results demonstrate a biologically important activity of manassantin in the control of complex I-mediated respiration and its profound effects on oxygen utilization, energy homeostasis, and glucose metabolism in mammalian cells.

show abstract

Section: Manassantin Inhibits Complex I and Bioenergetic Activitymentioning

confidence: 99%

The lignan manassantin is a potent and specific inhibitor of mitochondrial complex I and bioenergetic activity in mammals

Min

Oh³

et al. 2017

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…The XF24 instrument detects small changes in oxygen levels within the media immediately surrounding tissue. This is achieved by creating a transient <10 μL microchamber in which changes in oxygen and pH can be measured non-invasively, sensitively, and repeatedly over time (Ferrick et al 2008). The OCR was measured for each replicate liver sample in islet plates (Seahorse Biosciences) three times over the course of 15 minutes and the average OCR was calculated for each treatment.…”

Section: Mitochondrial Bioenergetics and Massmentioning

confidence: 99%

Hepatic transcriptomic and metabolic responses of hybrid striped bass (Morone saxatilis×Morone chrysops) to acute and chronic hypoxic insult

Beck

Fuller

et al. 2016

Comparative Biochemistry and Physiology Part D: Genomics and Pr

View full text Add to dashboard Cite

Striped bass (Morone saxatilis), white bass (Morone chrysops), and their hybrid are an important group of fish prized for recreational angling in the United States, and there and abroad as a high-value farmed fish. Regardless of habitat, it is not uncommon for fish of the genus Morone to encounter and cope with conditions of scarce oxygen availability. Previously, we determined that hybrid striped bass reared under conditions of chronic hypoxia exhibited reduced feed intake, lower lipid and nutrient retention, and poor growth. To better understand the molecular mechanisms governing these phenotypes, in the present study, we examined the transcriptomic profiles of hepatic tissue in hybrid striped bass exposed to chronic hypoxia (90days at 25% oxygen saturation) and acute hypoxia (6h at 25% oxygen saturation). Using high-throughput RNA-seq, we found that over 1400 genes were differentially expressed under disparate oxygen conditions, with the vast majority of transcriptional changes occurring in the acute hypoxia treatment. Gene pathway and bioenergetics analyses revealed hypoxia-mediated perturbation of genes and gene networks related to lipid metabolism, cell death, and changes in hepatic mitochondrial content and cellular respiration. This study offers a more comprehensive view of the temporal and tissue-specific transcriptional changes that occur during hypoxia, and reveals new and shared mechanisms of hypoxia tolerance in teleosts.

show abstract

The Evolution of Mitochondrial Toxicity Assessment in Industry

Hynes

Will

2018

Mitochondrial Biology and Experimental Therapeutics

View full text Add to dashboard Cite

Mitochondrial Dysfunction Assessed Quantitatively in Real Time by Measuring the Extracellular Flux of Oxygen and Protons

Cited by 3 publications

References 22 publications

The lignan manassantin is a potent and specific inhibitor of mitochondrial complex I and bioenergetic activity in mammals

The lignan manassantin is a potent and specific inhibitor of mitochondrial complex I and bioenergetic activity in mammals

Hepatic transcriptomic and metabolic responses of hybrid striped bass (Morone saxatilis×Morone chrysops) to acute and chronic hypoxic insult

The Evolution of Mitochondrial Toxicity Assessment in Industry

Contact Info

Product

Resources

About