K572R mutation of Miro1 affects its ubiquitination by Parkin upon mitochondrial depolarization Dzhamilja Safiulina, Malle Kuum, Vinay Choubey, Nana Gogichaishvili, Allen Kaasik Department of Pharmacology, University of Tartu, Estonia
E3 ligase Parkin along with PTEN-induced putative kinase Pink1 regulates mitochondrial trafficking and quarantines damaged mitochondria by disrupting their connection to the microtubules via Miro1, a key component of the mitochondrial motor complex. Recently lysine K572 in Miro1 C-terminal GTPase has been shown as a prioritized site for Parkin ubiqutination. Here we aimed to study a potential functional role of this modification. We first tested whether K572 mutation of Miro1 affects its ubiquitination upon mitochondrial depolarization. Co-immunoprecipitation experiments demonstrate that K572R mutant of Miro1 is not ubiquitinated as efficiently as wild type Miro1 after treatment with antimycin, oligomycin and MG132. Overexpression of both wild type Miro1 and K572R mutant induced Parkin translocation to mitochondria, while mitochondria sustained their rod shaped structures. We will further study whether Miro1 K572R could rescue the defect in mitochondrial motility and dynamics induced by silencing of Miro proteins in primary neuronal cultures. Altogether these experiments suggest that ubiquitination of Miro1 has a functional significance which needs more detailed studies.
Funding. This work was supported by grants from the Estonian Research Council (IUT2-5), the European Regional Development Fund (Project No. 2014-2020.4.01.15-0012) and from the European Union's Horizon 2020 research and innovation programme under grant agreement 692202. VC was supported by grant PUT513 from the Estonian Research Council
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