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Science Forum Index » Life Extension Forum » Glutathionylation of complex I increases superoxide formatio
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| Tim |
 Posted: Fri Jan 02, 2004 10:28 am |
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Reversible glutathionylation of complex I increases mitochondrial
superoxide formation.
Taylor ER, Hurrell F, Shannon RJ, Lin TK, Hirst J, Murphy MP.
Medical Research Council-Dunn Human Nutrition Unit, Wellcome Trust-MRC
Bldg., Hills Rd., Cambridge CB2 2XY, United Kingdom.
Increased production of reactive oxygen species (ROS) by mitochondria
is involved in oxidative damage to the organelle and in committing
cells to apoptosis or senescence, but the mechanisms of this increase
are unknown. Here we show that ROS production by mitochondrial complex
I increases in response to oxidation of the mitochondrial glutathione
pool. This correlates with thiols on the 51- and 75-kDa subunits of
complex I forming mixed disulfides with glutathione. Glutathionylation
of complex I increases superoxide production by the complex, and when
the mixed disulfides are reduced, superoxide production returns to
basal levels. Within intact mitochondria oxidation of the glutathione
pool to glutathione disulfide also leads to glutathionylation of
complex I, which correlates with increased superoxide formation. In
this case, most of this superoxide is converted to hydrogen peroxide,
which can then diffuse into the cytoplasm. This mechanism of
reversible mitochondrial ROS production suggests how mitochondria
might regulate redox signaling and shows how oxidation of the
mitochondrial glutathione pool could contribute to the pathological
changes that occur to mitochondria during oxidative stress.
PMID: 12649289 [PubMed - indexed for MEDLINE]
Full Text
http://www.jbc.org/cgi/content/full/278/22/19603
Tim |
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