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FEATURE:
Toby Reynolds
From small things
BMJ 2007; 335: 747-748 [Full text]
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[Read Rapid Response] Chemical toxicity and mitochondria
Heikki Savolainen   (12 October 2007)

Chemical toxicity and mitochondria 12 October 2007
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Heikki Savolainen,
Professor
Dept. of Occup. Safety & Hlth., FIN-33101 Tampere, Finland

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Re: Chemical toxicity and mitochondria

Dear Editor,

This excellent feature on mitochondria contains much of the current concepts. I would like to add that the organelle, and especially its repiratory chain, is an important target of toxic compounds.

The classic examples include inhibitors of the cytochrome oxidase at the terminal of the chain. It catalyzes the formation of water and is inhibited e.g. by cyanide, hydrogen sulfide, azide or formic acid (1).

Other toxicologically important inhibitors target the succinate dehydrogenase activity at the complex II of the chain. They include e.g. malonate, 3-nitropropionic acid or alkoxyacetic acids, the end metabolites of ethylene glycol ethers (2). The latter is particularly interesting as it leads to an accumulation of succinate which interferes with the degradation of hypoxia inducible factor 1-alpha (HIF-1) which plays a role in malignant transformation (3).

Thus, mitochondrial physiology and biology are important current topics in many fields of study.

1. Savolainen H. Biological monitoring of hydrogen sulfide exposure. Biol Monit, 1991; 1: 27-33.

2. Liesivuori J, Laitinen J, Savolainen H. Rat model for renal effects of 2-alkoxyalcohols and their acetates. Arch Toxicol, 1999; 73: 229-232.

3. Brière JJ, Favier J, Benit P. Mitochondrial succinate is instrumental for HIF 1 lapha translocation in SDHA-mutant fibroblasts under normoxicconditions. Hum Mol Genet, 2005; 14: 3263-3269.

Competing interests: None declared