Applications in Screening

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App Notes & Tech Briefs

Screening for Mitochondrial Biogenesis and Toxicity

A sensitive and robust cell-based screening assay.

Mitochondrial damage compromises ATP production and consequentially cellular viability. Given the central role that mitochondria play in regulating cellular function, drugs that undermine mitochondrial function frequently elicit toxic effects...
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Publications

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Advances in measuring cellular bioenergetics using extracellular flux
Ferrick D A, Neilson A and Beeson C
Drug Discov Today; 2008 Mar 1. 13 (40669):268-274.
In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone, trazodone, and buspirone
Dykens J A, Jamieson J D, Marroquin L D, Nadanaciva S, Xu J J, Dunn M C, Smith A R and Will Y
Toxicol Sci; 2008 Jun 1. 103 (2):335-345.
Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro
Dykens J A, Jamieson J, Marroquin L, Nadanaciva S, Billis P A and Will Y
Toxicol Appl Pharmacol; 2008 Dec 1. 233 (2):203-210.
A computational screen for regulators of oxidative phosphorylation implicates SLIRP in mitochondrial RNA homeostasis
Baughman J M, Nilsson R, Gohil V M, Arlow D H, Gauhar Z and Mootha V K
PLoS Genet; 2009 Aug 1. 5 (8):e1000590.
Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis
Gohil V M, Sheth S A, Nilsson R, Wojtovich A P, Lee J H, Perocchi F, Chen W, Clish C B, Ayata C, Brookes P S and Mootha V K
Nat Biotechnol; 2010 Mar 1. 28 (3):249-255.
A high-throughput respirometric assay for mitochondrial biogenesis and toxicity
Beeson C C, Beeson G C and Schnellmann R G
Anal Biochem; 2010 Sep 1. 404 (1):75-81.
9-oxo-10(E),12(E)-octadecadienoic acid derived from tomato is a potent PPAR α agonist to decrease triglyceride accumulation in mouse primary hepatocytes
Kim Y I, Hirai S, Takahashi H, Goto T, Ohyane C, Tsugane T, Konishi C, Fujii T, Inai S, Iijima Y, Aoki K, Shibata D, Takahashi N and Kawada T
Mol Nutr Food Res. 2010 Nov 18; [Epub ahead of print].

Technical Posters

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Analysis of glycolytic flux as a rapid screen to identify low lactate producing CHO cell lines with desirable monoclonal antibody yield and glycan profile
Legmann R, Melito J, Belzer I, Ferrick D
ESACT (European Society for Animal Cell Technology)
May 15-18, 2011
Vienna Austria

Webinars

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Using Reserve Capacity to Screen for Mitochondrial Toxicities and Biogenesis
Craig C. Beeson, PhD, Medical University of South Carolina
March 23, 2011

Preclinical screening for drug-induced mitochondrial dysfunction can predict toxicity and reduce attrition (or late stage failure) during drug development. Some new drugs may reach the market and their toxicity may not be discovered until many patients have been exposed. The unpredicted toxicity is due to the drug's adverse effects on mitochondrial function.

The XF Analyzer can facilitate preclinical drug evaluation for potential mitochondrial toxicity, addressing the issue early in the drug development process. The XF Analyzer generates data that can provide new understanding in relation to mitochondrial dysfunction, by allowing the measurement of cellular metabolism in real-time, in a microplate. By measuring the oxygen consumption rate (OCR)—a measure of mitochondrial respiration; as well as the extracellular acidification rate (ECAR)—a measure of glycolysis, you will be provided with the most physiologically relevant in vitro measurement for your bioenergetic studies.