Mitochondria, oxidative stress, and antioxidant defences
Lenaz, G.; Bovina, C.; Formiggini, G.; Parenti Castelli, G.
Acta Biochimica Polonica 46(1): 1-21
1999
ISSN/ISBN: 0001-527X PMID: 10453977 Document Number: 499379
Mitochondria are strongly involved in production of reactive oxygen species, considered today as the main pathogenic agent of many diseases. A vicious circle of oxidative stress and damage to cellular structures can lead to either cell death by apoptosis or to a cellular energetic decline and ageing. The early involvement of mitochondria in apoptosis includes expression of pro-apoptotic factors, release of cytochrome c from the inter-membrane space and opening of the permeability transition pore: cytochrome c release appears to precede pore opening. The mitochondrial theory of ageing considers somatic mutations (deletions) of mitochondrial DNA induced by oxygen radicals as the primary cause of energy decline; experimentally, Complex I appears to be mostly affected. We have developed the Pasteur effect (enhancement of lactate production by mitochondrial inhibition) as a bio-marker of mitochondrial bioenergetics in human platelets, and found it to be decreased in aged individuals. Cells counteract oxidative stress by antioxidants; among lipophilic antioxidants coenzyme Q is the only one of endogenous biosynthesis; exogenous coenzyme Q, however, may protect cells from oxidative stress in vivo.