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Dev Cell. 2016 Apr 18;37(2):174-189. doi: 10.1016/j.devcel.2016.03.023.

Polo Kinase Phosphorylates Miro to Control ER-Mitochondria Contact Sites and Mitochondrial Ca(2+) Homeostasis in Neural Stem Cell Development.

Lee S#1,2, Lee KS#1,2, Huh S#1, Liu S1, Lee DY1, Hong SH2, Yu K2, Lu B1.

Author information

1
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
2
BioNanotechnology Research Center, Korea Research Institute of Biotechnology and Bioscience, Daejeon, 305-806, Korea.
#
Contributed equally

Abstract

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.

PMID:
27093086
PMCID:
PMC4839004
DOI:
10.1016/j.devcel.2016.03.023
[Indexed for MEDLINE]
Free PMC Article

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