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


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.

SUBMITTER: Lee S 

PROVIDER: S-EPMC4839004 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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

Lee Seongsoo S   Lee Kyu-Sun KS   Huh Sungun S   Liu Song S   Lee Do-Yeon DY   Hong Seung Hyun SH   Yu Kweon K   Lu Bingwei B  

Developmental cell 20160401 2


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.  ...[more]

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