Widely Used Antibiotics Affect Mitochondria
From plants to mice and human cells, tetracyclines lead to mitochondrial dysfunction in model organisms.
March 12, 2015
The tetracycline-controlled promoter system is a widely used tool to conditionally switch gene transcription on or off in the presence of the eponymous antibiotic. Adding tetracyclines to eukaryotic cells leads to altered mitochondrial genome translation and cellular respiration defects across five widely used eukaryotic model systems..
Two years ago, study coauthor Johan Auwerx, an energy metabolism researcher at the École Polytechnique Fédérale in Lausanne, Switzerland, and his colleagues observed that the tetracycline class of antibiotics, which target mitochondrial translation, led to an imbalance between mitochondrial and nuclear protein translation in both worms and mammalian cell lines. Expanding on this observation, the researchers have now shown that even low concentrations of tetracyclines can inhibit mitochondrial function and lead to changes in both mitochondrial and nuclear protein expression. Across four commonly used human cell lines, as little as 1 microgram of the drug per milliliter resulted in a decrease in cellular respiration, signaling impaired mitochondrial activity. Treatment with amoxicillin, an antibiotic that does not target protein synthesis in the mitochondria, did not lead to these effects. Further, genome-wide expression data showed global repression of mitochondrial protein synthesis in the presence of the tetracycline doxycycline.
Given their results, the researchers cautioned against widespread tetracycline use in livestock because of the potential repercussions for neighboring plant life and human health. “This aspect of some antibiotics . . . has been overlooked,” said study coauthor Riekelt Houtkooper, a molecular biologist who studies metabolic aging at the Laboratory Genetic Metabolic Diseases of the Academic Medical Center in the Netherlands. “There is a lot of interest in antibiotic resistance and on the effects of antibiotics on the microbiome, but the effects on mitochondria is a whole new angle.”
“Our guts contain 10 times more bacteria than cells but the mitochondria are even more abundant than the bacteria in our guts,” Houtkooper continued. “We need more studies to show how the environment is affected by antibiotics.”
Nunnari agreed. “The pervasive use of any drug class, as in the case of tetracyclines, should always raise concerns about the more global consequences,” she said. “As basic scientists, we don’t think about the global consequences of the use of this drug class enough. This [study] will raise awareness.”
Lees meer Bron: TheScientist