Lee, S., Lee, K.S., Huh, S., Liu, S., Lee, D.Y., Hong, S.H., Yu, K., Lu, B. (2016). Polo Kinase Phosphorylates Miro to Control ER-Mitochondria Contact Sites and Mitochondrial Ca(2+) Homeostasis in Neural Stem Cell Development.  Dev. Cell 37(2): 174--189.

FBrf0232092

Research paper

Mitochondria play central roles in buffering intracellular Ca(2+) transients. While basal mitochondrial Ca(2+) (Ca(2+)mito) is needed to maintain organellar physiology, Ca(2+)mito overload can lead to cell death. How Ca(2+)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 Ca(2+)mito homeostasis control, independent of its role in mitochondrial transport. Miro interacts with Ca(2+) transporters at the ER-mitochondria contact site (ERMCS). Its inactivation causes Ca(2+)mito depletion and metabolic impairment, whereas its overexpression results in Ca(2+)mito overload, mitochondrial morphology change, and apoptotic response. Both conditions impaired NSC lineage progression. Ca(2+)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 Ca(2+)mito homeostasis and how its dysregulation may affect NSC metabolism/development and contribute to disease.

PMC4839004 (PMC) (EuropePMC)