Journal
TRAFFIC
Volume 19, Issue 3, Pages 229-242Publisher
WILEY
DOI: 10.1111/tra.12549
Keywords
mathematical modelling; membrane protrusion; microtubule; MIRO1; organelle motility; peroxisome; proliferation
Categories
Funding
- Fundacao para a Ciencia e a Tecnologia [PTDC/BIABCM/118605/2010, SFRH/BD/81223/2011, SFRH/BPD/77619/2011]
- Wellcome Trust [WT097835MF, WT105618MA]
- Biotechnology and Biological Sciences Research Council [BB/K006231/1, BB/N01541X/1]
- Medical Research Council [MR/P022405/1]
- Biotechnology and Biological Sciences Research Council [BB/N01541X/1, BB/K006231/1] Funding Source: researchfish
- Medical Research Council [MR/P022405/1] Funding Source: researchfish
- Fundação para a Ciência e a Tecnologia [SFRH/BD/81223/2011] Funding Source: FCT
- BBSRC [BB/K006231/1, BB/N01541X/1] Funding Source: UKRI
- MRC [MR/P022405/1] Funding Source: UKRI
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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 Mitochondrial Rho GTPase 1 (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.
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