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Developmental Cell

By May 1, 2018Stem Cells

Developmental Cell

Seongsoo Lee, Kyu-Sun Lee, Sungun Huh, Seung Hyun Hong, Kweon Yu, Bingwei Lu

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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