Role of Mitochondrial Dysfunction in Linezolid-Induced Lactic Acidosis

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Lactic acidosis can develop during linezolid use. When no other risk factors can be identified, it possibly reflects mitochondrial dysfunction induced by linezolid. This chapter examines the role of mitochondrial impairment in the etiology of linezolid-induced lactic acidosis, with a special emphasis on critically ill subjects who are at higher risk of death. Lactic acidosis in critically ill subjects commonly develops due to tissue hypoxia and thus mainly reflects lactate overproduction via accelerated glycolysis. Linezolid inhibits bacterial growth by interfering with bacterial protein synthesis, as do many other antibiotics. Insights into the mechanisms responsible for the therapeutic effects of oxazolidinones are important to understand the potential mitochondrial toxicity of these antibiotics. Intra-mitochondrial translation of messenger RNAs (mRNAs) into proteins relies on transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) that are encoded by mitochondrial DNA (mtDNA). mtDNA sequence polymorphisms can influence the individual response to specific drugs.

Original languageEnglish
Title of host publicationMitochondrial Dysfunction Caused by Drugs and Environmental Toxicants
Publisherwiley
Pages547-558
Number of pages12
Volume2-2
ISBN (Electronic)9781119329725
ISBN (Print)9781119329701
DOIs
Publication statusPublished - Feb 21 2018

Keywords

  • Intra-mitochondrial translation
  • Linezolid-induced lactic acidosis
  • Mitochondrial DNA sequence polymorphisms
  • Mitochondrial dysfunction
  • Mitochondrial toxicity
  • Therapeutic effects
  • Tissue hypoxia

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Santini, A., Ronchi, D., Piga, D., & Protti, A. (2018). Role of Mitochondrial Dysfunction in Linezolid-Induced Lactic Acidosis. In Mitochondrial Dysfunction Caused by Drugs and Environmental Toxicants (Vol. 2-2, pp. 547-558). wiley. https://doi.org/10.1002/9781119329725.ch36