|
ИСТИНА |
Войти в систему Регистрация |
ИСТИНА ЦЭМИ РАН |
||
pH-dependent substrate preference of pig heart lipoamide dehydrogenase varies with oligomeric state - Response to mitochondrial matrix acidificationстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Klyachko N.L., Shchedrina V.A., Efimov A.V., Kazakov S.V., Gazaryan I.G., Kristal B.S., Brown A.M.
- Журнал: Journal of Biological Chemistry
- Том: 280
- Номер: 16
- Год издания: 2005
- Издательство: American Society for Biochemistry and Molecular Biology Inc.
- Местоположение издательства: United States
- Первая страница: 16106
- Последняя страница: 16114
- DOI: 10.1074/jbc.M414285200
- Аннотация: Cycling of intracellular pH has recently been shown to play a critical role in ischemia-reperfusion injury. Ischemia-reperfusion also leads to mitochondrial matrix acidification and dysfunction. However, the mechanism by which matrix acidification contributes to mitochondrial dysfunction, oxidative stress, and the resultant cellular injury has not been elucidated. We observe pH-dependent equilibria between monomeric, dimeric, and a previously undescribed tetrameric form of pig heart lipoamide dehydrogenase (LADH), a mitochondrial matrix enzyme. Dynamic light scattering studies of native LADH in aqueous solution indicate that lowering pH favors a shift in average molecular mass from higher oligomeric states to monomer. Sedimentation velocity of LADH entrapped in reverse micelles reveals dimer and tetramer at both pH 5.8 and 7.5, but monomer was observed only at pH 5.8. Enzyme activity measurements in reverse Aerosol OT micelles in octane indicate that LADH dimer and tetramer possess lipoamide dehydrogenase and diaphorase activities at pH 7.5. Upon acidification to pH 5.8 only the LADH monomer is active and only the diaphorase activity is observed. These results indicate a correlation between pH-dependent changes in the LADH reaction specificity and its oligomeric state. The acidification of mitochondrial matrix that occurs during ischemia-reperfusion injury is sufficient to alter the structure and enzymatic specificity of LADH, thereby reducing mitochondrial defenses, increasing oxidative stress, and slowing the recovery of energy metabolism. Matrix acidification may also disrupt the quaternary structure of other mitochondrial protein complexes critical for cellular homeostasis and survival.
- Добавил в систему: Клячко Наталья Львовна