FOXD1-dependent MICU1 expression regulates mitochondrial activity and cell differentiation

Santhanam Shanmughapriya, Dhanendra Tomar, Zhiwei Dong, Katherine J. Slovik, Neeharika Nemani, Kalimuthusamy Natarajaseenivasan, Edmund Carvalho, Christy Lu, Kaitlyn Corrigan, Venkata Naga Srikanth Garikipati, Jessica Ibetti, Sudarsan Rajan, Carlos Barrero, Kurt Chuprun, Raj Kishore, Salim Merali, Ying Tian, Wenli Yang, Madesh Muniswamy

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Although many factors contribute to cellular differentiation, the role of mitochondria Ca2+ dynamics during development remains unexplored. Because mammalian embryonic epiblasts reside in a hypoxic environment, we intended to understand whether mCa2+ 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 mCa2+ 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 cCa2+ oscillations and promoted cellular differentiation and maturation. These findings establish a role of mCa2+ dynamics in regulation of cellular differentiation and reveal a molecular mechanism underlying this contribution through differential regulation of MICU1.

Original languageEnglish (US)
Article number3449
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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