Akt mediated mitochondrial protection in the heart: metabolic and survival pathways to the rescue.
Akt mediated mitochondrial protection in the heart: metabolic and survival pathways to the rescue.
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DOI：
10.1007/s10863-009-9205-y
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发表时间：
2009-04
影响因子：
3
通讯作者：
Brown, Joan Heller
中科院分区：
文献类型：
--
作者：
Miyamoto, Shigeki;Murphy, Anne N.;Brown, Joan Heller
心肌细胞死亡现在被认为是心脏病发展的关键因素。线粒体不仅负责能量产生以确保心输出量满足身体的能量需求，而且它们还是细胞生存信号的关键整合者。已知许多应激源可通过线粒体失调介导的坏死和/或凋亡来诱导细胞死亡。抗凋亡和促凋亡 Bcl-2 家族蛋白通过控制线粒体外膜通透性来调节细胞凋亡，而线粒体通透性转换孔 (PT-pore) 的开放会诱导内膜大幅通透性并随后导致外膜破裂。 Akt 是最受描述的由受体配体激活的生存激酶之一，其激活可保持线粒体完整性并保护心肌细胞免遭坏死和凋亡。 Akt 介导的线粒体保护机制尚未完全阐明。然而，越来越多的证据表明，通过转录和转录后机制招募的多个 Akt 靶分子可直接影响并保护线粒体。在这篇综述中，我们讨论了 Akt 激活影响线粒体变化的机制，从而保护心肌细胞并减弱心脏的病理生理反应。
Cardiomyocyte death is now recognized as a critical factor in the development of heart disease. Mitochondria are not only responsible for energy production to ensure that cardiac output meets the body’s energy demands, but they serve as critical integrators of cell survival signals. Numerous stressors are known to induce cell death by necrosis and/or apoptosis mediated through mitochondrial dysregulation. Anti- and pro-apoptotic Bcl-2 family proteins regulate apoptosis by controlling mitochondrial outer membrane permeability, whereas opening of the mitochondrial permeability transition pore (PT-pore) induces large amplitude permeability of the inner membrane and consequent rupture of the outer membrane. Akt is one of the best described survival kinases activated by receptor ligands and its activation preserves mitochondrial integrity and protects cardiomyocytes against necrotic and apoptotic death. The mechanisms responsible for Akt-mediated mitochondrial protection have not been fully elucidated. There is, however, accumulating evidence that multiple Akt target molecules, recruited through both transcriptional and post-transcriptional mechanisms, directly impinge upon and protect mitochondria. In this review we discuss mechanisms by which Akt activation can effect changes at the mitochondria that protect cardiomyocytes and attenuate pathophysiological responses of the heart.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
4.7
作者：
Bijur, GN;Jope, RS
通讯作者：
Jope, RS
DOI：
10.1016/s0022-2828(02)00310-3
发表时间：
2003-02-01
影响因子：
5
作者：
Bell, RM;Yellon, DM
通讯作者：
Yellon, DM
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
4.8
作者：
Basso, Emy;Petronilli, Valeria;Bernardi, Paolo
通讯作者：
Bernardi, Paolo