한빛사논문
Abstract
Seongsoo Lee,1,2,3,4 Kyu-Sun Lee,1,2,3 Sungun Huh,1,3 Song Liu,1 Do-Yeon Lee,1 Seung Hyun Hong,2 Kweon Yu,2 and Bingwei Lu1,*
1Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA
2BioNanotechnology Research Center, Korea Research Institute of Biotechnology and Bioscience, Daejeon 34141, Korea
3Co-first author
4Present address: Gwangju Center, Korea Basic Science Institute, Gwangju 61186, Korea
*Correspondence: Bingwei Lu
Summary
Mitochondria play central roles in buffering intracellular Ca2+ transients. While basal mitochondrial Ca2+ (Ca2+mito) is needed to maintain organellar physiology, Ca2+mito overload can lead to cell death. How Ca2+mito homeostasis is regulated is not well understood. Here we show that Miro, a known component of the mitochondrial transport machinery, regulates Drosophila neural stem cell (NSC) development through Ca2+mito homeostasis control, independent of its role in mitochondrial transport. Miro interacts with Ca2+ transporters at the ER-mitochondria contact site (ERMCS). Its inactivation causes Ca2+mito depletion and metabolic impairment, whereas its overexpression results in Ca2+mito overload, mitochondrial morphology change, and apoptotic response. Both conditions impaired NSC lineage progression. Ca2+mito homeostasis is influenced by Polo-mediated phosphorylation of a conserved residue in Miro, which positively regulates Miro localization to, and the integrity of, ERMCS. Our results elucidate a regulatory mechanism underlying Ca2+mito homeostasis and how its dysregulation may affect NSC metabolism/development and contribute to disease.
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