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Mitochondria deficient in complex I activity are depolarized by hydrogen peroxide in nerve terminals: relevance to Parkinson's disease
Author(s) -
Chinopoulos Christos,
AdamVizi Vera
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00060.x
Subject(s) - rotenone , hydrogen peroxide , mitochondrion , dopaminergic , oxidative stress , parkinson's disease , chemistry , oxidative phosphorylation , biophysics , membrane potential , electron transport complex i , respiratory chain , mitochondrial respiratory chain , dopamine , biochemistry , neuroscience , medicine , biology , disease
Deficiency of complex I in the respiratory chain and oxidative stress induced by hydrogen peroxide occur simultaneously in dopaminergic neurones in Parkinson's disease. Here we demonstrate that the membrane potential of in situ mitochondria (ΔΨm), as measured by the fluorescence change of JC‐l (5,5′,6,6′‐tetrachloro‐1,1,3,3′‐tetraethylbenzimidazolyl‐carbocyanine iodide), collapses when isolated nerve terminals are exposed to hydrogen peroxide (H 2 O 2 ,100 and 500 µ m ) in combination with the inhibition of complex I by rotenone (5 n m −1 µ m ). H 2 O 2 reduced the activity of complex I by 17%, and the effect of H 2 O 2 and rotenone on the enzyme was found to be additive. A decrease in ΔΨm induced by H 2 O 2 was significant when the activity of complex I was reduced to a similar extent as found in Parkinson's disease (26%). The loss of ΔΨm observed in the combined presence of complex I deficiency and H 2 O 2 indicates that when complex I is partially inhibited, mitochondria in nerve terminals become more vulnerable to H 2 O 2 ‐induced oxidative stress. This mechanism could be crucial in the development of bioenergetic failure in Parkinson's disease.