ArticlePloS one2013
Oxidative stress induced mitochondrial protein kinase A mediates cytochrome c oxidase dysfunction.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 61 citations in OpenAlex.
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- Contribution of Mitochondria to Insulin Secretion by Various Secretagogues.Antioxidants & redox signaling · 2022Review
- Physiological and pathological roles of protein kinase A in the heart.Cardiovascular research · 2022Review
- Casein Kinase 2 Signaling in White Matter Stroke.Frontiers in molecular biosciences · 2022Review
- Peptide Correlation Analysis (PeCorA) Reveals Differential Proteoform Regulation.Journal of proteome research · 2021Article
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- Oxidation of Protein Kinase A Regulatory Subunit PKARIα Protects Against Myocardial Ischemia-Reperfusion Injury by Inhibiting Lysosomal-Triggered Calcium Release.Circulation · 2021Article
- The Pancreatic β-Cell: The Perfect Redox System.Antioxidants (Basel, Switzerland) · 2021Review
- Mitochondrial Kinases and the Role of Mitochondrial Protein Phosphorylation in Health and Disease.Life (Basel, Switzerland) · 2021Review
- Chronic Inhibition of mROS Protects Against Coronary Endothelial Dysfunction in Mice With Diabetes.Frontiers in cell and developmental biology · 2021Article
- Insight into the Interactome of Intramitochondrial PKA Using Biotinylation-Proximity Labeling.International journal of molecular sciences · 2020Article
- Cardiac ischemia-reperfusion injury induces ROS-dependent loss of PKA regulatory subunit RIα.American journal of physiology. Heart and circulatory physiology · 2019Article
- Interplay between BMPs and Reactive Oxygen Species in Cell Signaling and Pathology.Biomolecules · 2019Review
- Phosphorylation of OXPHOS Machinery Subunits: Functional Implications in Cell Biology and Disease.The Yale journal of biology and medicine · 2019Review
- Pathobiological mechanisms underlying metabolic syndrome (MetS) in chronic obstructive pulmonary disease (COPD): clinical significance and therapeutic strategies.Pharmacology & therapeutics · 2019Review
- CK2 inhibition protects white matter from ischemic injury.Neuroscience letters · 2018Review
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
Previously we showed that Protein kinase A (PKA) activated in hypoxia and myocardial ischemia/reperfusion mediates phosphorylation of subunits I, IVi1 and Vb of cytochrome c oxidase. However, the mechanism of activation of the kinase under hypoxia remains unclear. It is also unclear if hypoxic stress activated PKA is different from the cAMP dependent mitochondrial PKA activity reported under normal physiological conditions. In this study using RAW 264.7 macrophages and in vitro perfused mouse heart system we investigated the nature of PKA activated under hypoxia. Limited protease treatment and digitonin fractionation of intact mitochondria suggests that higher mitochondrial PKA activity under hypoxia is mainly due to increased sequestration of PKA Catalytic α (PKAα) subunit in the mitochondrial matrix compartment. The increase in PKA activity is independent of mitochondrial cAMP and is not inhibited by adenylate cyclase inhibitor, KH7. Instead, activation of hypoxia-induced PKA is dependent on reactive oxygen species (ROS). H89, an inhibitor of PKA activity and the antioxidant Mito-CP prevented loss of CcO activity in macrophages under hypoxia and in mouse heart under ischemia/reperfusion injury. Substitution of wild type subunit Vb of CcO with phosphorylation resistant S40A mutant subunit attenuated the loss of CcO activity and reduced ROS production. These results provide a compelling evidence for hypoxia induced phosphorylation as a signal for CcO dysfunction. The results also describe a novel mechanism of mitochondrial PKA activation which is independent of mitochondrial cAMP, but responsive to ROS.
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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.