ArticlePloS one2013
Cytochrome C is tyrosine 97 phosphorylated by neuroprotective insulin treatment.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- Narrative review of rationale for IV deferoxamine plus intranasal insulin to ameliorate brain damage following resuscitation from cardiac arrest.Resuscitation plus · 2026Review
- Inhibitory Infrared Light Attenuates Mitochondrial Hyperactivity and Accelerates Restoration of Mitochondrial Homeostasis in an Oxygen-Glucose Deprivation/Reoxygenation Model.Antioxidants (Basel, Switzerland) · 2025Article
- Tyrosine 67 Phosphorylation Controls Respiration and Limits the Apoptotic Functions of CytochromeCells · 2025Article
- Cardiac Tyrosine 97 Phosphorylation of CytochromeInternational journal of molecular sciences · 2025Article
- Prostate Cancer-Specific Lysine 53 Acetylation of CytochromeBiomolecules · 2024Article
- Diverse functions of cytochrome c in cell death and disease.Cell death and differentiation · 2024Review
- Phosphorylations and Acetylations of CytochromeCells · 2024Review
- A review of stress-induced hyperglycaemia in the context of acute ischaemic stroke: Definition, underlying mechanisms, and the status of insulin therapy.Frontiers in neurology · 2023Review
- De novo sequencing and construction of a unique antibody for the recognition of alternative conformations of cytochromeProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mitochondrial Management of Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2021Review
- Lysine 53 Acetylation of CytochromeCells · 2021Article
- Mitochondrial Function and Parkinson's Disease: From the Perspective of the Electron Transport Chain.Frontiers in molecular neuroscience · 2021Review
- Post-Translational Modifications of CytochromeInternational journal of molecular sciences · 2020Review
- Nrf2/HO-1 mediates the neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury in rats.Disease models & mechanisms · 2020Article
- Article
- Stress signalling dynamics of the mitochondrial electron transport chain and oxidative phosphorylation system in higher plants.Annals of botany · 2020Review
- Non-invasive treatment with near-infrared light: A novel mechanisms-based strategy that evokes sustained reduction in brain injury after stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Cytochrome c phosphorylation: Control of mitochondrial electron transport chain flux and apoptosis.The international journal of biochemistry & cell biology · 2020Article
- Exploring protein phosphorylation by combining computational approaches and biochemical methods.Computational and structural biotechnology journal · 2020Article
- Wheel and Deal in the Mitochondrial Inner Membranes: The Tale of CytochromeOxidative medicine and cellular longevity · 2020Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Recent advancements in isolation techniques for cytochrome c (Cytc) have allowed us to discover post-translational modifications of this protein. We previously identified two distinct tyrosine phosphorylated residues on Cytc in mammalian liver and heart that alter its electron transfer kinetics and the ability to induce apoptosis. Here we investigated the phosphorylation status of Cytc in ischemic brain and sought to determine if insulin-induced neuroprotection and inhibition of Cytc release was associated with phosphorylation of Cytc. Using an animal model of global brain ischemia, we found a ∼50% decrease in neuronal death in the CA1 hippocampal region with post-ischemic insulin administration. This insulin-mediated increase in neuronal survival was associated with inhibition of Cytc release at 24 hours of reperfusion. To investigate possible changes in the phosphorylation state of Cytc we first isolated the protein from ischemic pig brain and brain that was treated with insulin. Ischemic brains demonstrated no detectable tyrosine phosphorylation. In contrast Cytc isolated from brains treated with insulin showed robust phosphorylation of Cytc, and the phosphorylation site was unambiguously identified as Tyr97 by immobilized metal affinity chromatography/nano-liquid chromatography/electrospray ionization mass spectrometry. We next confirmed these results in rats by in vivo application of insulin in the absence or presence of global brain ischemia and determined that Cytc Tyr97-phosphorylation is strongly induced under both conditions but cannot be detected in untreated controls. These data suggest a mechanism whereby Cytc is targeted for phosphorylation by insulin signaling, which may prevent its release from the mitochondria and the induction of apoptosis.
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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.