The role of mitochondria in pharmacotoxicology: a reevaluation of an old, newly emerging topic.

Roberto Scatena, Patrizia Bottoni, Giorgia Botta, Giuseppe Ettore Martorana, Bruno Giardina

Risultato della ricerca: Contributo in rivistaArticolo in rivista

140 Citazioni (Scopus)

Abstract

In addition to their well-known critical role in energy metabolism, mitochondria are now recognized as the location where various catabolic and anabolic processes, calcium fluxes, various oxygen-nitrogen reactive species, and other signal transduction pathways interact to maintain cell homeostasis and to mediate cellular responses to different stimuli. It is important to consider how pharmacological agents affect mitochondrial biochemistry, not only because of toxicological concerns but also because of potential therapeutic applications. Several potential targets could be envisaged at the mitochondrial level that may underlie the toxic effects of some drugs. Recently, antiviral nucleoside analogs have displayed mitochondrial toxicity through the inhibition of DNA polymerase-gamma (pol-gamma). Other drugs that target different components of mitochondrial channels can disrupt ion homeostasis or interfere with the mitochondrial permeability transition pore. Many known inhibitors of the mitochondrial electron transfer chain act by interfering with one or more of the respiratory chain complexes. Nonsteroidal anti-inflammatory drugs (NSAIDs), for example, may behave as oxidative phosphorylation uncouplers. The mitochondrial toxicity of other drugs seems to depend on free radical production, although the mechanisms have not yet been clarified. Meanwhile, drugs targeting mitochondria have been used to treat mitochondrial dysfunctions. Importantly, drugs that target the mitochondria of cancer cells have been developed recently; such drugs can trigger apoptosis or necrosis of the cancer cells. Thus the aim of this review is to highlight the role of mitochondria in pharmacotoxicology, and to describe whenever possible the main molecular mechanisms underlying unwanted and/or therapeutic effects.
Lingua originaleEnglish
pagine (da-a)12-21
Numero di pagine10
RivistaAMERICAN JOURNAL OF PHYSIOLOGY. CELL PHYSIOLOGY
Stato di pubblicazionePubblicato - 2007

Keywords

  • metabolism
  • mitochondria
  • pharmacotoxicology

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