Researchers at the University of Exeter say they have discovered how the movement and membrane dynamics of peroxisomes are mediated. These organelles fulfill critical protective functions in the cell and are vital for health, according to the scientists, who add that the loss of peroxisome function and dynamics leads to severe developmental and neurological defects.
The team, which published its study (“A Role for MIRO1 in Motility and Membrane Dynamics of Peroxisomes”) in the journal Traffic, identified a protein called MIRO1 that plays a key role in attaching peroxisomes to motor proteins, allowing them to move within the cell.
“Peroxisomes are dynamic organelles which fulfil essential roles in lipid and ROS [reactive oxygen species] 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,” write the investigators.
“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.”
“In this study, we identified MIRO1 as the missing adaptor protein that links peroxisomes to molecular motors and revealed a new role for MIRO1 in peroxisome motility in mammalian cells,” said Michael Schrader, Ph.D., professor of cell biology at Exeter. “In addition, we used MIRO1 as a tool to generate pulling forces at peroxisomes in living cells.”
The research led to new insights into the molecular mechanisms determining peroxisome number and shape in the cell under normal and disease conditions. Altered numbers, different shapes, or different distributions of peroxisomes in patient cells are often a mark of peroxisomal disorders and understanding why this happens and how to modulate peroxisome numbers or distribution can provide new possibilities to improve cell performance in those patients, explained Dr. Schrader.
“This might also be relevant to age-related conditions like dementia, deafness, and blindness, as peroxisomes are known to have important protective functions within sensory cells,” he continued.
People with severe peroxisomal disorders, also known as Zellweger spectrum disorders, often die as children or young adults, and a charity called Zellweger UK exists to raise awareness and to support families and sufferers.