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Shanmughapriya S , Tomar D , Dong Z , Slovik KJ , Nemani N , Natarajaseenivasan K , Carvalho E , Lu C , Corrigan K , Garikipati VNS , Ibetti J , Rajan S , Barrero C , Chuprun K , Kishore R , Merali S , Tian Y , Yang W , Madesh M
FOXD1-dependent MICU1 expression regulates mitochondrial activity and cell differentiation
Nat Commun. 2018 Aug 29;9(1) :3449
PMID: 30158529    PMCID: PMC6115453   
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Although many factors contribute to cellular differentiation, the role of mitochondria Ca(2+) dynamics during development remains unexplored. Because mammalian embryonic epiblasts reside in a hypoxic environment, we intended to understand whether mCa(2+) and its transport machineries are regulated during hypoxia. Tissues from multiple organs of developing mouse embryo evidenced a suppression of MICU1 expression with nominal changes on other MCU complex components. As surrogate models, we here utilized human embryonic stem cells (hESCs)/induced pluripotent stem cells (hiPSCs) and primary neonatal myocytes to delineate the mechanisms that control mCa(2+) and bioenergetics during development. Analysis of MICU1 expression in hESCs/hiPSCs showed low abundance of MICU1 due to its direct repression by Foxd1. Experimentally, restoration of MICU1 established the periodic cCa(2+) oscillations and promoted cellular differentiation and maturation. These findings establish a role of mCa(2+) dynamics in regulation of cellular differentiation and reveal a molecular mechanism underlying this contribution through differential regulation of MICU1.
2041-1723 Shanmughapriya, Santhanam Tomar, Dhanendra ORCID: http://orcid.org/0000-0002-3144-7257 Dong, Zhiwei Slovik, Katherine J Nemani, Neeharika Natarajaseenivasan, Kalimuthusamy Carvalho, Edmund Lu, Christy Corrigan, Kaitlyn Garikipati, Venkata Naga Srikanth Ibetti, Jessica Rajan, Sudarsan ORCID: http://orcid.org/0000-0003-4096-0586 Barrero, Carlos Chuprun, Kurt Kishore, Raj Merali, Salim Tian, Ying Yang, Wenli Madesh, Muniswamy Journal Article England Nat Commun. 2018 Aug 29;9(1):3449. doi: 10.1038/s41467-018-05856-4.