TY - JOUR
T1 - Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species
AU - Storz, Peter
AU - Döppler, Heike
AU - Toker, Alex
PY - 2005/10
Y1 - 2005/10
N2 - Efficient elimination of mitochondrial reactive oxygen species (mROS) correlates with increased cellular survival and organism life span. Detoxification of mitochondrial ROS is regulated by induction of the nuclear SOD2 gene, which encodes the manganese-dependent superoxide dismutase (MnSOD). However, the mechanisms by which mitochondrial oxidative stress activates cellular signaling pathways leading to induction of nuclear genes are not known. Here we demonstrate that release of mROS activates a signal relay pathway in which the serine/threonine protein kinase D (PKD) activates the NF-κB transcription factor, leading to induction of SOD2. Conversely, the FOXO3a transcription factor is dispensable for mROS-induced SOD2 induction. PKD-mediated MnSOD expression promotes increased survival of cells upon release of mROS, suggesting that mitochondrion-to-nucleus signaling is necessary for efficient detoxification mechanisms and cellular viability.
AB - Efficient elimination of mitochondrial reactive oxygen species (mROS) correlates with increased cellular survival and organism life span. Detoxification of mitochondrial ROS is regulated by induction of the nuclear SOD2 gene, which encodes the manganese-dependent superoxide dismutase (MnSOD). However, the mechanisms by which mitochondrial oxidative stress activates cellular signaling pathways leading to induction of nuclear genes are not known. Here we demonstrate that release of mROS activates a signal relay pathway in which the serine/threonine protein kinase D (PKD) activates the NF-κB transcription factor, leading to induction of SOD2. Conversely, the FOXO3a transcription factor is dispensable for mROS-induced SOD2 induction. PKD-mediated MnSOD expression promotes increased survival of cells upon release of mROS, suggesting that mitochondrion-to-nucleus signaling is necessary for efficient detoxification mechanisms and cellular viability.
UR - http://www.scopus.com/inward/record.url?scp=25444449225&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=25444449225&partnerID=8YFLogxK
U2 - 10.1128/MCB.25.19.8520-8530.2005
DO - 10.1128/MCB.25.19.8520-8530.2005
M3 - Article
C2 - 16166634
AN - SCOPUS:25444449225
SN - 0270-7306
VL - 25
SP - 8520
EP - 8530
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 19
ER -