Abstract
Mitochondria play a central role in the life and death of cells. They are not\r\nmerely the centre for energy metabolism, but are also the headquarters for\r\ndifferent catabolic and anabolic processes, calcium fluxes, and various\r\nsignalling pathways. Mitochondria maintain homeostasis in the cell by interacting\r\nwith reactive oxygen-nitrogen species and responding adequately to different\r\nstimuli. In this context, the interaction of pharmacological agents with\r\nmitochondria is an aspect of molecular biology that is too often disregarded, not\r\nonly in terms of toxicology but also from a therapeutic point of view, especially\r\nconsidering the potential therapeutic applications related to the modulation of\r\nmitochondrial activity.At the mitochondrial level, there are several potential\r\ndrug targets that can lead to toxicity, but only for few of them, a real clinical\r\ncounterpart has been demonstrated. Recently, antiviral nucleoside analogues have \r\nshown mitochondrial toxicity through the inhibition of DNA polymerase-gamma.\r\nOther drugs targeted to different components of the mitochondrial channels can\r\ndisrupt ion homeostasis or affect the mitochondrial permeability transition pore.\r\nMany molecules are known inhibitors of the mitochondrial electron transport\r\nchain, interfering with one or more of the complexes in the respiratory chain.\r\nSome drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), may lead to\r\nuncoupling of oxidative phosphorylation, while the mitochondrial toxicity of\r\nother drugs seems to depend on the production of free radicals, although this\r\nmechanism has yet to be defined. Besides toxicity, other drugs have been targeted\r\nto mitochondria to treat mitochondrial dysfunctions. Many drugs have been\r\nrecently developed to target the mitochondria of cancer cells in order to trigger\r\napoptosis or necrosis. The aim of this chapter is to underline the role of\r\nmitochondria in pharmacology and toxicology, stressing all the potential\r\ntherapeutic approaches being due to iatrogenic modulation of the multitude of\r\nmitochondrial activities.
Lingua originale | Inglese |
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pagine (da-a) | 329-346 |
Numero di pagine | 18 |
Rivista | Advances in Experimental Medicine and Biology |
Volume | 942 |
Numero di pubblicazione | 942 |
DOI | |
Stato di pubblicazione | Pubblicato - 2012 |
Pubblicato esternamente | Sì |
All Science Journal Classification (ASJC) codes
- Biochimica, Genetica, Biologia Molecolare Generali
Keywords
- mitochondria