Inhibition of mTOR Prevents ROS Production Initiated by Ethidium Bromide-Induced Mitochondrial DNA Depletion.
Inhibition of mTOR Prevents ROS Production Initiated by Ethidium Bromide-Induced Mitochondrial DNA Depletion.
复制标题
DOI：
10.3389/fendo.2014.00122
复制
发表时间：
2014
影响因子：
5.2
通讯作者：
Sell C
中科院分区：
文献类型：
--
作者：
Nacarelli T;Azar A;Sell C
The regulation of mitochondrial mass and DNA content involves a complex interaction between mitochondrial DNA replication machinery, functional components of the electron transport chain, selective clearance of mitochondria, and nuclear gene expression. In order to gain insight into cellular responses to mitochondrial stress, we treated human diploid fibroblasts with ethidium bromide at concentrations that induced loss of mitochondrial DNA over a period of 7 days. The decrease in mitochondrial DNA was accompanied by a reduction in steady state levels of the mitochondrial DNA binding protein, TFAM, a reduction in several electron transport chain protein levels, increased mitochondrial and total cellular ROS, and activation of p38 MAPK. However, there was an increase in mitochondrial mass and voltage dependent anion channel levels. In addition, mechanistic target of rapamycin (mTOR) activity, as judged by p70S6K targets, was decreased while steady state levels of p62/SQSTM1 and Parkin were increased. Treatment of cells with rapamycin created a situation in which cells were better able to adapt to the mitochondrial dysfunction, resulting in decreased ROS and increased cell viability but did not prevent the reduction in mitochondrial DNA. These effects may be due to a more efficient flux through the electron transport chain, increased autophagy, or enhanced AKT signaling, coupled with a reduced growth rate. Together, the results suggest that mTOR activity is affected by mitochondrial stress, which may be part of the retrograde signal system required for normal mitochondrial homeostasis.
登录
查看更多内容
影响因子：
7.8
作者：
Miller RA;Harrison DE;Astle CM;Fernandez E;Flurkey K;Han M;Javors MA;Li X;Nadon NL;Nelson JF;Pletcher S;Salmon AB;Sharp ZD;Van Roekel S;Winkleman L;Strong R
通讯作者：
Strong R
影响因子：
3.6
作者：
Ghosh, Sangeeta;Patel, Nishant;Swerdlow, Russell H.
通讯作者：
Swerdlow, Russell H.
影响因子：
7.8
作者：
Davis, AF;Clayton, DA
通讯作者：
Clayton, DA
DOI：
10.1196/annals.1395.025
发表时间：
2007-01-01
期刊：
BIOGERONTOLOGY: MECHANISMS AND INTERVENTIONS
影响因子：
--
作者：
Olgun, Abdullah;Akman, Serif
通讯作者：
Akman, Serif
影响因子：
3.9
作者：
Huang J;Manning BD
通讯作者：
Manning BD