title: PKD1 protein is involved in reactive oxygen species-mediated mitochondrial depolarization in cooperation with protein kinase Cδ (PKCδ).
abstract: In this study, we used gene targeting in mice to identify the in vivo functions of PKD1. In addition to phenotypically characterizing the resulting knock-out animals, we also used mouse embryonic fibroblasts to investigate the associated signaling pathways in detail. This study is the first to use genetic deletion to reveal that PKD1 is a key regulator involved in determining the threshold of mitochondrial depolarization that leads to the production of reactive oxygen species. In addition, we also provide clear evidence that PKCδ is upstream of PKD1 in this process and acts as the activating kinase of PKD1. Therefore, our in vivo data indicate that PKD1 functions not only in the context of aging but also during nutrient deprivation, which occurs during specific phases of tumor growth.
authors.affiliation: From the Biotechnology Centre of Oslo, University of Oslo, 0349 Oslo, Norway.
authors.forename: Thianzhou
authors.initials: T
authors.lastname: Zhang
authors.affiliation: From the Biotechnology Centre of Oslo, University of Oslo, 0349 Oslo, Norway.
authors.forename: Philip
authors.initials: P
authors.lastname: Sell
authors.affiliation: From the Biotechnology Centre of Oslo, University of Oslo, 0349 Oslo, Norway.
authors.forename: Ursula
authors.initials: U
authors.lastname: Braun
authors.affiliation: From the Biotechnology Centre of Oslo, University of Oslo, 0349 Oslo, Norway michael.leitges@biotek.uio.no.
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D061251:Primary Cell Culture; D051745:Protein Kinase C-delta / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D050396:TRPP Cation Channels / Q000172:deficiency / Q000235:genetics*
chemical_list: D006861:Hydrogen Peroxide; D051745:Protein Kinase C-delta; D017382:Reactive Oxygen Species; D050396:TRPP Cation Channels
keywords: Cell Signaling; Gene Knockout; Mitochondrial Apoptosis; Protein Kinase C (PKC); Protein Kinase D (PKD); Reactive Oxygen Species (ROS)