A role for MIRO1 in motility and membrane dynamics of peroxisomes
© 2018 Wiley
Reason for embargo
Under embargo until 24 January 2019 in compliance with publisher policy
Peroxisomes are dynamic organelles which fulfil essential roles in lipid and ROS metabolism. Peroxisome movement and positioning allows interaction with other organelles and is crucial for their cellular function. In mammalian cells, such movement is microtubule-dependent and mediated by kinesin and dynein motors. The mechanisms of motor recruitment to peroxisomes are largely unknown, as well as the role this plays in peroxisome membrane dynamics and proliferation. Here, using a combination of microscopy, live-cell imaging analysis and mathematical modelling, we identify a role for the Ras GTPase MIRO1 as an adaptor for microtubule-dependent peroxisome motility in mammalian cells. We show that MIRO1 is targeted to peroxisomes and alters their distribution and motility. Using a peroxisome-targeted MIRO1 fusion protein, we demonstrate that MIRO1-mediated pulling forces contribute to peroxisome membrane elongation and proliferation in cellular models of peroxisome disease. Our findings reveal a molecular mechanism for establishing peroxisome-motor protein associations in mammalian cells and provide new insights into peroxisome membrane dynamics in health and disease.
We thank all colleagues who provided cell lines, plasmids and antibodies (see Tables S1-S4). This work was supported by BBSRC (BB/K006231/1, BB/N01541X/1) and FCT (PTDC/BIA-BCM/118605/2010) to MS; DMR, MS and JM were supported by a Wellcome Trust Institutional Strategic Support Award (WT105618MA; WT097835MF) and DMR by the Medical Research Council (MR/P022405/1). DR and AG were supported by personal fellowship grants from the Portuguese Foundation for Science and Technology (FCT) (SFRH/BPD/77619/2011; SFRH/BD/81223/2011) under the scope of “Programa Operacional Temático Factores de Competitividade” (COMPETE) of “Quadro Comunitário de Apoio III” and co-financed by Fundo Comunitário Europeu (FEDER). The authors declare no conflict of interest.
This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record
Published online 24 January 2018