Related Experiment Video

Updated: Jul 22, 2026

Synthesis and Evaluation of a Ruthenium-based Mitochondrial Calcium Uptake Inhibitor
07:12

Synthesis and Evaluation of a Ruthenium-based Mitochondrial Calcium Uptake Inhibitor

Published on: October 26, 2017

Inhibition of mammalian mitochondrial protein synthesis by oxazolidinones

E E McKee1, M Ferguson, A T Bentley

  • 1Indiana University School of Medicine--South Bend, IN 46617, USA. McKee.6@nd.edu

Antimicrobial Agents and Chemotherapy
|May 26, 2006
PubMed

Insights

Oxazolidinone antibiotics, including linezolid, inhibit mitochondrial protein synthesis in mammals. This mitochondrial toxicity is a key consideration for developing new oxazolidinone antibiotics.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Toxicology

Background:

  • Oxazolidinones are a class of synthetic antibiotics with a unique mechanism of action targeting bacterial protein synthesis.
  • Concerns exist regarding potential off-target effects of antibiotics on host cellular processes.
  • Mitochondrial protein synthesis is crucial for cellular energy production and is a potential target for drug toxicity.

Purpose of the Study:

  • To investigate the effects of various oxazolidinones, including linezolid, on mammalian mitochondrial protein synthesis.
  • To compare the mitochondrial inhibitory effects of oxazolidinones with other classes of antibiotics.
  • To assess the relationship between antibacterial potency and mitochondrial toxicity within the oxazolidinone class.

Main Methods:

  • Intact mitochondria were isolated from rat heart and liver, and rabbit heart and bone marrow.
  • The inhibition of mitochondrial protein synthesis was measured in the presence of different oxazolidinones.
  • Comparative analysis was performed with other antibiotics known to inhibit bacterial protein synthesis, such as chloramphenicol, tetracycline, macrolides, lincosamides, and aminoglycosides.

Main Results:

  • Oxazolidinones, as a class, demonstrated significant inhibition of mammalian mitochondrial protein synthesis across all tested tissues.
  • Antibacterial potency of oxazolidinones correlated directly with their potency in inhibiting mitochondrial protein synthesis.
  • Chloramphenicol and tetracycline also inhibited mitochondrial protein synthesis, while macrolides, lincosamides, and aminoglycosides did not.

Conclusions:

  • Inhibition of mammalian mitochondrial protein synthesis is a general characteristic of the oxazolidinone class of antibiotics.
  • The findings highlight the necessity of evaluating potential mitochondrial toxicity during the development of novel oxazolidinone-based therapeutics.
  • Understanding these off-target effects is critical for ensuring the safety and efficacy of future antibiotic agents.

More Related Videos

Rapid Isolation of the Mitoribosome from HEK Cells09:33

Rapid Isolation of the Mitoribosome from HEK Cells

Published on: October 4, 2018

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources10:24

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources

Published on: January 27, 2026

Related Concept Videos

Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Inhibitors of Bacterial DNA Synthesis01:28

Inhibitors of Bacterial DNA Synthesis

Bacterial pathogens depend on precise and efficient DNA replication to sustain infection. Two type II topoisomerases—DNA gyrase and topoisomerase IV—are critical to this process, as they resolve DNA supercoiling and unlink chromosomes during replication. Fluoroquinolones, synthetic derivatives of quinolones, exploit this mechanism by stabilizing the transient DNA–enzyme cleavage complex, preventing strand religation, and causing lethal double-strand breaks. These antibiotics are selectively...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...