MICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration
| العنوان: | MICU1 regulation of mitochondrial Ca2+ uptake dictates survival and tissue regeneration |
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| المؤلفون: | Melanie Paillard, György Hajnóczky, Emanuel Rubin, Egle Juskeviciute, Anil Noronha Antony, Jan B. Hoek, Cynthia Moffat, Brad Bolon, Erin L. Seifert, György Csordás, Jason M. Correnti |
| المساهمون: | Mitocare-Thomas Jefferson University-Philadelphia, Thomas Jefferson University [Philadelphia, PA, USA] |
| المصدر: | Nature Communications Nature Communications, Nature Publishing Group, 2016, 7 (1), ⟨10.1038/ncomms10955⟩ Nature Communications, Vol 7, Iss 1, Pp 1-10 (2016) |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Necrosis, Cell Survival, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Physiology, chemistry.chemical_element, Mitochondria, Liver, Mitochondrion, Calcium, Mitochondrial Membrane Transport Proteins, Article, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, Mitochondrial membrane transport protein, Calcium-binding protein, medicine, Hepatectomy, Animals, Humans, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Multidisciplinary, biology, Mitochondrial Permeability Transition Pore, Regeneration (biology), Calcium-Binding Proteins, General Chemistry, Liver regeneration, Liver Regeneration, Mitochondria, Cell biology, Mice, Inbred C57BL, 030104 developmental biology, Liver, Mitochondrial permeability transition pore, chemistry, Hepatocytes, biology.protein, Female, medicine.symptom |
| الوصف: | Mitochondrial Ca2+ uptake through the recently discovered Mitochondrial Calcium Uniporter (MCU) is controlled by its gatekeeper Mitochondrial Calcium Uptake 1 (MICU1). However, the physiological and pathological role of MICU1 remains unclear. Here we show that MICU1 is vital for adaptation to postnatal life and for tissue repair after injury. MICU1 knockout is perinatally lethal in mice without causing gross anatomical defects. We used liver regeneration after partial hepatectomy as a physiological stress response model. Upon MICU1 loss, early priming is unaffected, but the pro-inflammatory phase does not resolve and liver regeneration fails, with impaired cell cycle entry and extensive necrosis. Ca2+ overload-induced mitochondrial permeability transition pore (PTP) opening is accelerated in MICU1-deficient hepatocytes. PTP inhibition prevents necrosis and rescues regeneration. Thus, our study identifies an unanticipated dependence of liver regeneration on MICU1 and highlights the importance of regulating MCU under stress conditions when the risk of Ca2+ overload is elevated. Mitochondrial calcium uptake is a highly regulated process, and calcium overload can lead to cell death. Here, using knockout mouse model, the authors show that the mitochondrial calcium uniporter (MCU) regulator MICU1 is needed to prevent calcium overload and promotes survival under liver regeneration and postnatal adaptation-associated stress. |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::be4887974e1e263a038d968048b09929 https://doi.org/10.1038/ncomms10955 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....be4887974e1e263a038d968048b09929 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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