Document Type
Article
Publication Date
3-9-2016
Abstract
Mitochondrial Ca(2+) 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. Ca(2+) 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 Ca(2+) overload is elevated.
Recommended Citation
Antony, Anil Noronha; Paillard, Melanie; Moffat, Cynthia; Juskeviciute, Egle; Correnti, Jason; Bolon, Brad; Rubin, MD, Emanual; Csordás, György; Seifert, Erin L; Hoek, Jan B.; and Hajnóczky, György, "MICU1 regulation of mitochondrial Ca(2+) uptake dictates survival and tissue regeneration." (2016). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 184.
https://jdc.jefferson.edu/pacbfp/184
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
26956930
Comments
This article has been peer reviewed. It was published in: Nature Communications.
Volume 7, 9 March 2016, Article number 10955.
The published version is available at DOI: 10.1038/ncomms10955
Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.
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