ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Two protein kinase C isoforms, δ and ε, regulate energy homeostasis in mitochondria by transmitting opposing signals to the pyruvate dehydrogenase complex.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Regulation of pyruvate dehydrogenase complex: Dancing to different drums in cancer.International journal of cancer · 2026Review
- The Role of Protein Kinase C During the Differentiation of Stem and Precursor Cells into Tissue Cells.Biomedicines · 2024Review
- 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
- Vitamin A Deficiency Alters the Phototransduction Machinery and Distinct Non-Vision-Specific Pathways in theBiomolecules · 2022Article
- p66Shc in Cardiovascular Pathology.Cells · 2022Review
- The mitochondrial PKCδ/retinol signal complex exerts real-time control on energy homeostasis.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- 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
- Host-pathogen interactions in malaria: cross-kingdom signaling and mitochondrial regulation.Current opinion in immunology · 2015Review
- Metformin Induces Cell Cycle Arrest and Apoptosis in Drug-Resistant Leukemia Cells.Leukemia research and treatment · 2015Article
- Coenzyme q and the respiratory chain: coenzyme q pool and mitochondrial supercomplexes.Molecular syndromology · 2014Article
- Regulation of pyruvate metabolism in metabolic-related diseases.Reviews in endocrine & metabolic disorders · 2014Review
- Mammalian metabolism of β-carotene: gaps in knowledge.Nutrients · 2013Review
- Isozyme-specific interaction of protein kinase Cδ with mitochondria dissected using live cell fluorescence imaging.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Energy production in mitochondria is a multistep process that requires coordination of several subsystems. While reversible phosphorylation is emerging as the principal tool, it is still unclear how this signal network senses the workloads of processes as different as fuel procurement, catabolism in the Krebs cycle, and stepwise oxidation of reducing equivalents in the electron transfer chain. We previously proposed that mitochondria use oxidized cytochrome c in concert with retinol to activate protein kinase Cδ, thereby linking a prominent kinase network to the redox balance of the ETC. Here, we show that activation of PKCε in mitochondria also requires retinol as a cofactor, implying a redox-mechanism. Whereas activated PKCδ transmits a stimulatory signal to the pyruvate dehdyrogenase complex (PDHC), PKCε opposes this signal and inhibits the PDHC. Our results suggest that the balance between PKCδ and ε is of paramount importance not only for flux of fuel entering the Krebs cycle but for overall energy homeostasis. We observed that the synthetic retinoid fenretinide substituted for the retinol cofactor function but, on chronic use, distorted this signal balance, leading to predominance of PKCε over PKCδ. The suppression of the PDHC might explain the proapoptotic effect of fenretinide on tumor cells, as well as the diminished adiposity observed in experimental animals and humans. Furthermore, a disturbed balance between PKCδ and PKCε might underlie the injury inflicted on the ischemic myocardium during reperfusion. dehydrogenase complex.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.