Hexokinase II dissociation alone cannot account for changes in heart mitochondrial function, morphology and sensitivity to permeability transition pore opening following ischemia
| العنوان: | Hexokinase II dissociation alone cannot account for changes in heart mitochondrial function, morphology and sensitivity to permeability transition pore opening following ischemia |
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| المؤلفون: | Gonçalo C. Pereira, Tatyana N Andrienko, Joanne E. Parker, Nadiia Rawlings, Laura Lee, Johanna Ouwendijk, Jeremy M. Henley, Andrew P. Halestrap |
| المساهمون: | Pereira, Gonçalo C [0000-0001-9638-0615], Lee, Laura [0000-0002-7974-6803], Halestrap, Andrew P [0000-0001-5374-2778], Apollo - University of Cambridge Repository |
| المصدر: | PLoS ONE, Vol 15, Iss 6, p e0234653 (2020) PLoS ONE C. Pereira, G, Lee, L J, Rawlings, N, Ouwendijk, J, Parker, J E, Andrienko, T N, Henley, J M & Halestrap, A P 2020, ' Hexokinase II dissociation alone cannot account for changes in heart mitochondrial function, morphology and sensitivity to permeability transition pore opening following ischemia ', PLoS ONE, vol. 15, no. 6, e0234653 . https://doi.org/10.1371/journal.pone.0234653Test |
| بيانات النشر: | Public Library of Science (PLoS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Critical Care and Emergency Medicine, Light, Myocardial Ischemia, 030204 cardiovascular system & hematology, Mitochondrion, Ligands, Biochemistry, Vascular Medicine, Mitochondrial Dynamics, Mitochondrial Membrane Transport Proteins, Mitochondria, Heart, Scattering, 0302 clinical medicine, Ischemia, Hexokinase, Medicine and Health Sciences, Ischemic Preconditioning, Inner mitochondrial membrane, Energy-Producing Organelles, Multidisciplinary, biology, Chemistry, Physics, Electromagnetic Radiation, Cytochrome c, Eukaryota, Heart, Hematology, Hydrogen-Ion Concentration, Mitochondria, Insects, Physical Sciences, Mitochondrial Membranes, Medicine, Mitochondrial fission, Cellular Structures and Organelles, Anatomy, Research Article, Protein Binding, Dynamins, Arthropoda, Imaging Techniques, Science, Cell Respiration, Glucose-6-Phosphate, Bioenergetics, Research and Analysis Methods, 03 medical and health sciences, medicine, Animals, Inner membrane, cardiovascular diseases, Rats, Wistar, Ants, Mitochondrial Permeability Transition Pore, Morphometry, Organisms, Light Scattering, Hemodynamics, Biology and Life Sciences, Cell Biology, medicine.disease, Invertebrates, Hymenoptera, 030104 developmental biology, Mitochondrial permeability transition pore, Reperfusion, Cardiovascular Anatomy, Biophysics, biology.protein, Ischemic preconditioning, Reperfusion injury |
| الوصف: | We previously demonstrated that hexokinase II (HK2) dissociation from mitochondria during cardiac ischemia correlates with cytochrome c (cyt-c) loss, oxidative stress and subsequentreperfusion injury. However, whether HK2 release is the primary signal mediating this ischemia-induced mitochondrial dysfunction was not established. To investigate this, we studied the effects of dissociating HK2 from isolated heart mitochondria. Mitochondria isolated from Langendorff-perfused rat hearts before and after 30 min global ischemia ± ischemic preconditioning (IPC) were subject to in vitro dissociation of HK2 by incubation with glucose-6-phosphate at pH 6.3. Prior HK2 dissociation from pre- or end-ischemic heart mitochondria had no effect on their cyt-c release, respiration (± ADP) or mitochondrial permeability transition pore (mPTP) opening. Inner mitochondrial membrane morphology was assessed indirectly by monitoring changes in light scattering (LS) and confirmed by transmission electron microscopy. Although no major ultrastructure differences were detected between pre- andend-ischemia mitochondria, the amplitude of changes in LS was reduced in the latter. This was prevented by IPC but not mimicked in vitro by HK2 dissociation. We also observed more Drp1, a mitochondrial fission protein, in end-ischemia mitochondria. IPC failed to prevent this increase but did decrease mitochondrial-associated dynamin 2. In vitro HK2 dissociation alone cannot replicate ischemia-induced effects on mitochondrial function implying that in vivo dissociation of HK2 modulates end-ischemia mitochondrial function indirectly perhaps involving interaction with mitochondrial fission proteins. The resulting changes in mitochondrial morphology and cristae structure would destabilize outer / inner membrane interactions, increase cyt-c release and enhance mPTP sensitivity to [Ca2+]. |
| وصف الملف: | application/zip; text/xml; application/pdf |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee5c155b9d7bde5355823ba5ea97d2a8Test https://doi.org/10.1371/journal.pone.0234653Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ee5c155b9d7bde5355823ba5ea97d2a8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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