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- Polo kinase phosphorylates Miro to control ER-mitochondria contact sites and mitochondrial Ca2+ homeostasis in neural stem cell development
- 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
- 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.
- Elsevier-Cell Press
- Appears in Collections:
- Division of Biomaterials Research > Bionanotechnology Research Center > 1. Journal Articles
Division of Biomedical Research > Disease Target Structure Research Center > 1. Journal Articles
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