FOXD1-dependent MICU1 expression regulates mitochondrial activity and cell differentiation

作者：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 A. Barrero, Kurt Chuprun, Raj Kishore, Salim Merali, Ying Tian, Wenli Yang, Muniswamy Madesh · 发表于：Nature Communications · 年份：2018 · DOI：10.1038/s41467-018-05856-4 · 被引用次数：45 · 研究领域：Mitochondrial Function and Pathology、ATP Synthase and ATPases Research、Adipose Tissue and Metabolism

Abstract 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 m Ca 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 m Ca 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 c Ca 2+ oscillations and promoted cellular differentiation and maturation. These findings establish a role of m Ca 2+ dynamics in regulation of cellular differentiation and reveal a molecular mechanism underlying this contribution through differential regulation of MICU1.