Mitochondrial diacylglycerol initiates protein-kinase-D1-mediated ROS signaling

Catherine F. Cowell, Heike Döppler, Irene K. Yan, Angelika Hausser, Yoshio Umazawa, Peter Storz

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Increases in reactive oxygen species (ROS) have been implicated in age-related diseases, including cancer. The serine/threonine kinase protein kinase D1 (PKD1) is a stress-responsive kinase and sensor for reactive oxygen species, which can initiate cell survival through NF-κB signaling. We have previously shown that in response to ROS, PKD1 is activated at the mitochondria. However, the initial signaling events leading to localization of PKD1 to the mitochondria are unknown. Here, we show that formation of mitochondrial diacylglycerol (DAG) and its binding to PKD1 is the means by which PKD1 is localized to the mitochondria in response to ROS. Interestingly, DAG to which PKD1 is recruited in this pathway is formed downstream of phospholipase D1 (PLD1) and a lipase-inactive PLD1 or inhibition of PLD1 by pharmacological inhibitors blocked PKD1 activation under oxidative stress. To date it has been viewed that monosaturated and saturated DAG formed via PLD1 have no signaling function. However, our data describe a role for PLD1-induced DAG as a competent second messenger at the mitochondria that relays ROS to PKD1-mediated mitochondria-to-nucleus signaling.

Original languageEnglish (US)
Pages (from-to)919-928
Number of pages10
JournalJournal of cell science
Issue number7
StatePublished - Apr 1 2009


  • DAG
  • Mitochondria
  • Oxidative stress
  • PKD
  • PLD
  • ROS

ASJC Scopus subject areas

  • Cell Biology


Dive into the research topics of 'Mitochondrial diacylglycerol initiates protein-kinase-D1-mediated ROS signaling'. Together they form a unique fingerprint.

Cite this