Miro1-mediated mitochondrial positioning supports subcellular redox status.
Miro1-mediated mitochondrial positioning supports subcellular redox status.
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Miro1介导的线粒体定位支持亚细胞氧化还原状态。
DOI：
10.1016/j.redox.2020.101818
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发表时间：
2021-01
期刊：
影响因子：
11.4
通讯作者：
Cunniff B
中科院分区：
文献类型：
--
作者：
Alshaabi H;Shannon N;Gravelle R;Milczarek S;Messier T;Cunniff B
线粒体通过微管马达、肌动蛋白细胞骨架和衔接蛋白的作用在整个细胞中进行战略性运输。线粒体的细胞内定位支持ATP、Ca 2+和活性氧物质（ROS，即过氧化氢，H2 O2）的亚细胞水平。我们小组以前的工作表明，线粒体适配蛋白Miro 1的缺失导致线粒体的核周聚集，使细胞周围缺乏线粒体，从而损害外周能量状态。在此，我们报告说，删除Miro 1显着限制亚细胞H2 O2水平的核周空间，直接影响细胞内的反应，线粒体活性氧升高。使用基因编码的H2 O2-响应的荧光生物传感器Hyper 7，我们表明，最高水平的亚细胞H2 O2映射到线粒体密度增加的网站。Miro 1缺失或Taxol破坏微管动力学可显著降低外周H2 O2水平。在用鱼藤酮抑制线粒体复合物1后，我们观察到细胞外周H2 O2的峰值升高以及线粒体过氧化物氧还蛋白3（PRX 3）和细胞溶质过氧化物氧还蛋白2（PRX 2）的互补氧化。相反，在缺乏Miro 1的细胞中，鱼藤酮不会增加外周H2 O2或PRX 2氧化，而是导致核H2 O2增加和DNA损伤反应升高。最后，局部Hyper 7氧化水平与MEFs中粘着斑（FA）的大小和丰度相关，与Miro 1 +/+ MEFs相比，缺乏Miro 1的细胞具有显著较小的粘着斑和降低的黏着斑蛋白和p130 Cas磷酸化水平。总之，我们提出的证据表明，线粒体的细胞内分布影响亚细胞H2 O2水平和依赖于线粒体ROS的局部细胞反应。
Mitochondria are strategically trafficked throughout the cell by the action of microtubule motors, the actin cytoskeleton and adapter proteins. The intracellular positioning of mitochondria supports subcellular levels of ATP, Ca2+ and reactive oxygen species (ROS, i.e. hydrogen peroxide, H2O2). Previous work from our group showed that deletion of the mitochondrial adapter protein Miro1 leads to perinuclear clustering of mitochondria, leaving the cell periphery devoid of mitochondria which compromises peripheral energy status. Herein, we report that deletion of Miro1 significantly restricts subcellular H2O2 levels to the perinuclear space which directly affects intracellular responses to elevated mitochondrial ROS. Using the genetically encoded H2O2-responsive fluorescent biosensor HyPer7, we show that the highest levels of subcellular H2O2 map to sites of increased mitochondrial density. Deletion of Miro1 or disruption of microtubule dynamics with Taxol significantly reduces peripheral H2O2 levels. Following inhibition of mitochondrial complex 1 with rotenone we observe elevated spikes of H2O2 in the cell periphery and complementary oxidation of mitochondrial peroxiredoxin 3 (PRX3) and cytosolic peroxiredoxin 2 (PRX2). Conversely, in cells lacking Miro1, rotenone did not increase peripheral H2O2 or PRX2 oxidation but rather lead to increased nuclear H2O2 and an elevated DNA-damage response. Lastly, local levels of HyPer7 oxidation correlate with the size and abundance of focal adhesions (FAs) in MEFs and cells lacking Miro1 have significantly smaller focal adhesions and reduced phosphorylation levels of vinculin and p130Cas compared to Miro1+/+ MEFs. Together, we present evidence that the intracellular distribution of mitochondria influences subcellular H2O2 levels and local cellular responses dependent on mitochondrial ROS.
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影响因子：
8.8
作者：
Debattisti V;Gerencser AA;Saotome M;Das S;Hajnóczky G
通讯作者：
Hajnóczky G
DOI：
10.1083/jcb.200601067
发表时间：
2006-05-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glater EE;Megeath LJ;Stowers RS;Schwarz TL
通讯作者：
Schwarz TL
影响因子：
--
作者：
AW, TY;JONES, DP
通讯作者：
JONES, DP
芒柄花素通过 KEAP1-NRF2-GSTP1 轴改善奥沙利铂诱导的周围神经病变
影响因子：
11.4
作者：
Fang, Yuan;Ye, Juan;Cao, Peng
通讯作者：
Cao, Peng
DOI：
10.1073/pnas.1500722112
发表时间：
2015-07-14
影响因子：
11.1
作者：
Caino, M. Cecilia;Ghosh, Jagadish C.;Altieri, Dario C.
通讯作者：
Altieri, Dario C.