ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2010
Regulation of intermediary metabolism by the PKCdelta signalosome in mitochondria.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Mitochondrial potassium channels: mitochondria-specific mechanism of regulation.Biophysical reviews · 2026Review
- MGlu5 Dependent Mitochondrial Translocation of PKCδ: A Mechanism Raising Astrocytic Oxidative Metabolism in Response to Extracellular Glutamate.Journal of neurochemistry · 2025Article
- Article
- PKCδ is an activator of neuronal mitochondrial metabolism that mediates the spacing effect on memory consolidation.bioRxiv : the preprint server for biology · 2024Article
- Reduced protein kinase C delta in a high molecular weight complex in mitochondria and elevated creatine uptake into Barth syndrome B lymphoblasts.Journal of translational genetics and genomics · 2024Article
- Counteracting Colon Cancer by Inhibiting Mitochondrial Respiration and Glycolysis with a Selective PKCδ Activator.International journal of molecular sciences · 2023Article
- Quantum chemistry rules retinoid biology.Communications biology · 2023Review
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- Insulin directly stimulates mitochondrial glucose oxidation in the heart.Cardiovascular diabetology · 2020Article
- The mitochondrial PKCδ/retinol signal complex exerts real-time control on energy homeostasis.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Mechanism and Treatment Related to Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy.Frontiers in molecular neuroscience · 2019Review
- Retinol saturase modulates lipid metabolism and the production of reactive oxygen species.Archives of biochemistry and biophysics · 2017Article
- Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies.International journal of molecular sciences · 2016Review
- P66Shc, a key regulator of metabolism and mitochondrial ROS production, is dysregulated by mouse embryo culture.Molecular human reproduction · 2016Article
- Retinol as a cofactor for PKCδ-mediated impairment of insulin sensitivity in a mouse model of diet-induced obesity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Retinol as electron carrier in redox signaling, a new frontier in vitamin A research.Hepatobiliary surgery and nutrition · 2016Review
- MicroRNAs Regulate Mitochondrial Function in Cerebral Ischemia-Reperfusion Injury.International journal of molecular sciences · 2015Review
- Metformin Induces Cell Cycle Arrest and Apoptosis in Drug-Resistant Leukemia Cells.Leukemia research and treatment · 2015Article
- Article
- PKCδ promotes high glucose induced renal tubular oxidative damage via regulating activation and translocation of p66Shc.Oxidative medicine and cellular longevity · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
PKCδ has emerged as a novel regulatory molecule of oxidative phosphorylation by targeting the pyruvate dehydrogenase complex (PDHC). We showed that activation of PKCδ leads to the dephosphorylation of pyruvate dehydrogenase kinase 2 (PDK2), thereby decreasing PDK2 activity and increasing PDH activity, accelerating oxygen consumption, and augmenting ATP synthesis. However, the molecular components that mediate PKCδ signaling in mitochondria have remained elusive so far. Here, we identify for the first time a functional complex, which includes cytochrome c as the upstream driver of PKCδ, and uses the adapter protein p66Shc as a platform with vitamin A (retinol) as a fourth partner. All four components are necessary for the activation of the PKCδ signal chain. Genetic ablation of any one of the three proteins, or retinol depletion, silences signaling. Furthermore, mutations that disrupt the interaction of cytochrome c with p66Shc, of p66Shc with PKCδ, or the deletion of the retinol-binding pocket on PKCδ, attenuate signaling. In cytochrome c-deficient cells, reintroduction of cytochrome c Fe(3+) protein restores PKCδ signaling. Taken together, these results indicate that oxidation of PKCδ is key to the activation of the pathway. The PKCδ/p66Shc/cytochrome c signalosome might have evolved to effect site-directed oxidation of zinc-finger structures of PKCδ, which harbor the activation centers and the vitamin A binding sites. Our findings define the molecular mechanisms underlying the signaling function of PKCδ in mitochondria.
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Registered trials
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