Polo kinase phosphorylates Miro to control ER-mitochondria contact sites and mitochondrial Ca2+ homeostasis in neural stem cell development

Cited 79 time in scopus
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Title
Polo kinase phosphorylates Miro to control ER-mitochondria contact sites and mitochondrial Ca2+ homeostasis in neural stem cell development
Author(s)
Seongsoo Lee; Kyu-Sun Lee; S Huh; S Liu; D Y Lee; Seung Hyun Hong; Kweon Yu; B Lu
Bibliographic Citation
Developmental Cell, vol. 37, no. 2, pp. 174-189
Publication Year
2016
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.
ISSN
1534-5807
Publisher
Elsevier-Cell Press
DOI
http://dx.doi.org/10.1016/j.devcel.2016.03.023
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > 1. Journal Articles
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