Independent roles of methionine sulfoxide reductase A in mitochondrial ATP synthesis and as antioxidant in retinal pigment epithelial cells.
Independent roles of methionine sulfoxide reductase A in mitochondrial ATP synthesis and as antioxidant in retinal pigment epithelial cells.
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DOI：
10.1016/j.freeradbiomed.2013.10.006
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发表时间：
2013-12
影响因子：
7.4
通讯作者：
Finnemann, Silvia C.
中科院分区：
文献类型：
--
作者：
Dun, Ying;Vargas, Jade;Brot, Nathan;Finnemann, Silvia C.
关键词：
抗氧化酶甲硫氨酸亚砜还原酶A（MsrA）在视网膜色素上皮（RPE）中高度表达，视网膜色素上皮是相邻光感受器的支持组织。MsrA蛋白水平与培养的RPE对实验性氧化应激的敏感性相关。为了研究MsrA是否以及如何影响RPE功能，无论氧化应激如何，我们测试了MsrA急性沉默或过表达对感光细胞外段片段（POS）吞噬作用的影响，这是一种对视力至关重要的RPE日常功能。内源性MsrA定位于培养的大鼠RPE的线粒体和胞浆。RPE细胞操纵表达更高或更低水平的MsrA比对照细胞没有表现出细胞死亡的迹象，但增加或减少，分别POS结合以及吞噬。这些影响改变MsrA蛋白浓度的吞噬作用是独立的氧化应激水平。然而，当线粒体呼吸被抑制时，改变MsrA表达对吞噬作用没有影响。此外，在使用线粒体氧化磷酸化进行ATP合成的RPE细胞中，ATP含量与MsrA蛋白水平直接相关，但在仅依赖糖酵解的RPE细胞中则不相关。过表达MsrA足以特异性增加呼吸链复合体IV的活性，而复合体II的活性和线粒体含量不受影响。因此，MsrA可能通过增加复合物-IV活性来增强ATP合成。MsrA对能量代谢的这种贡献独立于其保护免受升高的氧化应激的功能，但有助于RPE细胞对常规但重要的感光细胞的支持。
The antioxidant enzyme methionine sulfoxide reductase A (MsrA) is highly expressed in the retinal pigment epithelium (RPE), a support tissue for neighboring photoreceptors. MsrA protein levels correlate with sensitivity of RPE in culture to experimental oxidative stress. To investigate whether and how MsrA affects RPE functionality regardless of oxidative stress, we tested the effects of acute silencing or overexpression of MsrA on the phagocytosis of photoreceptor outer segment fragments (POS), a demanding, daily function of the RPE that is essential for vision. Endogenous MsrA localized to mitochondria and cytosol of rat RPE in culture. RPE cells manipulated to express higher or lower levels of MsrA than control cells showed no signs of cell death but increased or decreased, respectively, POS binding as well as engulfment. These effects of altered MsrA protein concentration on phagocytosis were independent of the levels of oxidative stress. However, altering MsrA expression had no effect on phagocytosis when mitochondrial respiration was inhibited. Furthermore, ATP content directly correlated with MsrA protein levels in RPE cells that used mitochondrial oxidative phosphorylation for ATP synthesis but not in RPE cells that relied on glycolysis alone. Overexpressing MsrA was sufficient to increase specifically the activity of complex-IV of the respiratory chain, while activity of complex-II and mitochondrial content were unaffected. Thus, MsrA likely enhances ATP synthesis by increasing complex-IV activity. Such contribution of MsrA to energy metabolism is independent of its function in protection from elevated oxidative stress but contributes to routine but vital photoreceptor support by RPE cells.
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DOI：
10.1084/jem.20041447
发表时间：
2004-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nandrot EF;Kim Y;Brodie SE;Huang X;Sheppard D;Finnemann SC
通讯作者：
Finnemann SC
DOI：
10.1073/pnas.0308215100
发表时间：
2004-02-03
影响因子：
11.1
作者：
Yermolaieva, O;Xu, R;Hoshi, T
通讯作者：
Hoshi, T
影响因子：
7.4
作者：
Zhao, Hang;Kim, Geumsoo;Liu, Chengyu;Levine, Rodney L.
通讯作者：
Levine, Rodney L.
DOI：
10.1073/pnas.94.18.9932
发表时间：
1997-09-02
影响因子：
11.1
作者：
Ciorba, MA;Heinemann, SH;Hoshi, T
通讯作者：
Hoshi, T
影响因子：
7.4
作者：
Yu, Chia-Chia;Nandrot, Emeline F.;Dun, Ying;Finnemann, Silvia C.
通讯作者：
Finnemann, Silvia C.