Sensing hypoxia by mitochondria : a unifying hypothesis involving S-nitrosation
Sensing hypoxia by mitochondria : a unifying hypothesis involving S-nitrosation
复制标题
通过线粒体感知缺氧：涉及 S-亚硝化的统一假说
DOI：
10.1089/ars.2012.4788
复制
发表时间：
2014
影响因子：
6.6
通讯作者：
Schildknecht S
中科院分区：
文献类型：
--
作者：
Ullrich V;Schildknecht S
Significance:Sudden hypoxia requires a rapid response in tissues with high energy demand. Mitochondria are rapid sensors for a lack of oxygen, but no consistent mechanism for the sensing process and the subsequent counter-regulation has been described.Recent Advances:In the present hypothesis review, we suggest an oxygen-sensing mechanism by mitochondria that is initiated at low oxygen tension by electrons from the respiratory chain, leading to the reduction of intracellular nitrite to nitric oxide (·NO) that would subsequently compete with oxygen for binding to cytochrome c oxidase. This allows superoxide (\documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$^{ \bullet}{ \rm O}_2^ -$$ \end{document}) formation in hypoxic areas, leading to S-nitrosation and the inhibition of mitochondrial Krebs cycle enzymes. With more formation of \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$^{ \bullet}{ \rm O}_2^ -$$ \end{document}, peroxynitrite is generated and known to damage the connection between the mitochondrial matrix and the outer membrane.Critical Issues:A fundamental question on a regulatory mechanism is its reversibility. Readmission of oxygen and opening of the mitochondrial KATP-channel would allow electrons from glycerol-3-phosphate to selectively reduce the ubiquinone pool to generate \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$^{ \bullet}{ \rm O}_2^ -$$ \end{document} at both sides of the inner mitochondrial membrane. On the cytosolic side, superoxide is dismutated and will support H2O2/Fe2+-dependent transcription processes and on the mitochondrial matrix side, it could lead to the one-electron reduction and reactivation of S-nitrosated proteins.Future Directions:It remains to be elucidated up to which stage the herein proposed silencing of mitochondria remains reversible and when irreversible changes that ultimately lead to classical reperfusion injury are initiated.Antioxid. Redox Signal.20, 325–338.
Significance:Sudden hypoxia requires a rapid response in tissues with high energy demand. Mitochondria are rapid sensors for a lack of oxygen, but no consistent mechanism for the sensing process and the subsequent counter-regulation has been described.Recent Advances:In the present hypothesis review, we suggest an oxygen-sensing mechanism by mitochondria that is initiated at low oxygen tension by electrons from the respiratory chain, leading to the reduction of intracellular nitrite to nitric oxide (•NO) that would subsequently compete with oxygen for binding to cytochrome c oxidase. This allows superoxide (\documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$^{ \bullet}{ \rm O}_2^ -$$ \end{document}) formation in hypoxic areas, leading to S-nitrosation and the inhibition of mitochondrial Krebs cycle enzymes. With more formation of \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$^{ \bullet}{ \rm O}_2^ -$$ \end{document}, peroxynitrite is generated and known to damage the connection between the mitochondrial matrix and the outer membrane.Critical Issues:A fundamental question on a regulatory mechanism is its reversibility. Readmission of oxygen and opening of the mitochondrial KATP-channel would allow electrons from glycerol-3-phosphate to selectively reduce the ubiquinone pool to generate \documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document} $$^{ \bullet}{ \rm O}_2^ -$$ \end{document} at both sides of the inner mitochondrial membrane. On the cytosolic side, superoxide is dismutated and will support H2O2/Fe2+-dependent transcription processes and on the mitochondrial matrix side, it could lead to the one-electron reduction and reactivation of S-nitrosated proteins.Future Directions:It remains to be elucidated up to which stage the herein proposed silencing of mitochondria remains reversible and when irreversible changes that ultimately lead to classical reperfusion injury are initiated.Antioxid. Redox Signal.20, 325–338.
登录
查看更多内容
过氧亚硝酸盐导致钙从线粒体流出，而环孢菌素 A 可以阻止钙流出
影响因子：
3.5
作者：
M. A. Packer;M. Murphy
通讯作者：
M. Murphy
参与能量稳态的激酶协同作用的分子方法。
影响因子：
3.9
作者：
D. Neumann;U. Schlattner;T. Wallimann
通讯作者：
T. Wallimann
影响因子：
37.8
作者：
Sasaki, N;Sato, T;Marbán, E
通讯作者：
Marbán, E
影响因子：
4.1
作者：
Iñarrea, P;Moini, H;Cadenas, E
通讯作者：
Cadenas, E
影响因子：
4.3
作者：
Aguirre, Enara;Rodriguez-Juarez, Felix;Cadenas, Susana
通讯作者：
Cadenas, Susana