Coenzyme q as the possible source of electrons for oxygen radicals
production during ca2+-stimulated oxidative damage of mitochondria.
Kowaltowski, Alicia J., Roger F. Castilho, and Anibal E. Vercesi.
Departamento de Bioqu[acute]imica, Instituto de Biologia, Universidade
Estadual de Campinas, Campinas (Brazil).
APStracts 2:0074C, 1995.
Rotenone-poisoned rat liver mitochondria energized by succinate addition,
after a 5 min period of pre-incubation in presence of 10 [mu]M Ca2+, produce
H2O2 at much faster rates, undergo extensive swelling and are not able to
retain the membrane potential and accumulated Ca2+. Similar results were
obtained when a suspension of rat liver mitochondria pre-incubated in
anaerobic medium during 5 min was reoxygenated. The addition of either EGTA,
ruthenium red, catalase or dithiothreitol, just prior to succinate or O2
addition, prevented mitochondrial swelling, indicating the involvement of
Ca2+, reactive oxygen species and oxidation of membrane protein thiols in
this process of membrane permeabilization. Inhibition of mitochondrial
swelling by cyclosporin A suggests that the membrane alterations observed
under these experimental conditions are related to opening of the
permeability transition pore. The presence of FCCP, which prevents Ca2+
cycling across the membrane, did not inhibit mitochondrial swelling when Ca2+
influx into the mitochondrial matrix was driven by a high Ca2+ gradient. When
rotenone plus antimycin A-poisoned mitochondria were energized by N,N,N',N'
-tetramethyl-p-phenylenediamine (TMPD), which reduces respiratory chain
complex IV, mitochondrial swelling did not occur, unless succinate, which
reduces coenzyme Q, was also added. It is concluded that reduced coenzyme Q
is the electron source for oxygen radicals production during Ca2+-stimulated
oxidative damage of mitochondria.
Received 18 April 1994; accepted in final form 13 January 1995.
APS Manuscript Number C205-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 28 February 1995.