The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts

Kao, Li-Pin, Ovchinnikov, Dmitry and Wolvetang, Ernst (2012) The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts. Toxicology and Applied Pharmacology, 261 1: 42-49. doi:10.1016/j.taap.2012.03.009


Author Kao, Li-Pin
Ovchinnikov, Dmitry
Wolvetang, Ernst
Title The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts
Journal name Toxicology and Applied Pharmacology   Check publisher's open access policy
ISSN 0041-008X
1096-0333
Publication date 2012-05
Sub-type Article (original research)
DOI 10.1016/j.taap.2012.03.009
Volume 261
Issue 1
Start page 42
End page 49
Total pages 8
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Collection year 2013
Language eng
Abstract The expression of mitochondrial components is controlled by an intricate interplay between nuclear transcription factors and retrograde signaling from mitochondria. The role of mitochondrial DNA (mtDNA) and mtDNA-encoded proteins in mitochondrial biogenesis is, however, poorly understood and thus far has mainly been studied in transformed cell lines. We treated primary human fibroblasts with ethidium bromide (EtBr) or chloramphenicol for six weeks to inhibit mtDNA replication or mitochondrial protein synthesis, respectively, and investigated how the cells recovered from these insults two weeks after removal of the drugs. Although cellular growth and mitochondrial gene expression were severely impaired after both inhibitor treatments we observed marked differences in mitochondrial structure, membrane potential, glycolysis, gene expression, and redox status between fibroblasts treated with EtBr and chloramphenicol. Following removal of the drugs we further detected clear differences in expression of both mtDNA-encoded genes and nuclear transcription factors that control mitochondrial biogenesis, suggesting that the cells possess different compensatory mechanisms to recover from drug-induced mitochondrial dysfunction. Our data reveal new aspects of the interplay between mitochondrial retrograde signaling and the expression of nuclear regulators of mitochondrial biogenesis, a process with direct relevance to mitochondrial diseases and chloramphenicol toxicity in humans.
Keyword Mitochondrial biogenesis
Mitochondrial rho minus cells
Transcription factors
Human foreskin fibroblast cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 27 March 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
Australian Institute for Bioengineering and Nanotechnology Publications
 
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Created: Thu, 10 May 2012, 16:10:15 EST by Associate Professor Ernst Wolvetang on behalf of Aust Institute for Bioengineering & Nanotechnology