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Methylene blue does not bypass Complex III antimycin block in mouse brain mitochondria
Author(s) -
Gureev Artem P.,
Shaforostova Ekaterina A.,
Popov Vasily N.,
Starkov Anatoly A.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13332
Subject(s) - mitochondrion , ubiquinol , methylene blue , antimycin a , chemistry , coenzyme q – cytochrome c reductase , biochemistry , cytochrome c , biophysics , microbiology and biotechnology , biology , photocatalysis , catalysis
Methylene blue ( MB ) is a promising prodrug to treat mitochondrial dysfunctions that is currently being used in clinical trials for Alzheimer's disease. MB can penetrate the blood brain barrier, accumulating in brain mitochondria where it acts as a redox mediator in the electron transfer chain (ETC). Mitochondrial flavins are thought to reduce MB , which is then oxidized by cytochrome c , thereby bypassing inhibited Complex I of ETC. We found that in mouse brain mitochondria, MB fails to restore the membrane potential and respiration inhibited by antimycin. Furthermore, antimycin inhibits MB ‐induced H 2 O 2 generation. Our data suggest that the acceptor of electrons from MB is a Qo ubiquinol‐binding site of Complex III ; thus, MB ‐based drugs might not be helpful in mitochondrial dysfunctions involving Complex III inhibition.