Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species

Peter Storz, Heike Döppler, Alex Toker

Research output: Contribution to journalArticle

157 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8520-8530
Number of pages11
JournalMolecular and Cellular Biology
Volume25
Issue number19
DOIs
StatePublished - Oct 2005

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Reactive Oxygen Species
Mitochondria
Superoxide Dismutase
Transcription Factors
Protein-Serine-Threonine Kinases
Genes
Signal Transduction
Cell Survival
Oxidative Stress
protein kinase D

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

Protein kinase D mediates mitochondrion-to-nucleus signaling and detoxification from mitochondrial reactive oxygen species. / Storz, Peter; Döppler, Heike; Toker, Alex.

In: Molecular and Cellular Biology, Vol. 25, No. 19, 10.2005, p. 8520-8530.

Research output: Contribution to journalArticle

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