Cell Biologists Discover How Peroxisomes and Endoplasmic Reticulum Associate and Work Together

Scientists have made a breakthrough in understanding how different organelles of human cells interact. Organelles are the functional units of a cell. Like organs in a body, they perform specialized functions. To allow survival of the cell, organelles have to interact and cooperate. How this is mediated and regulated in the cell is an important and challenging question in cell biology. Researchers at the University of Exeter (UK) have now discovered how two cell organelles - called peroxisomes and the endoplasmic reticulum (ER) - associate with each other at the molecular level and work together. This cooperation is crucial for the production of specific lipids, which are essential for the function of nerve cells and can protect cells from oxidative damage. Loss of peroxisome function leads to a range of severe or fatal disorders associated with developmental and neurological defects. "Close contacts between peroxisomes and the ER were observed more than 50 years ago in ultrastructural studies, but the molecular mechanism remained a mystery," said lead author Dr. Michael Schrader, of the University of Exeter. "This is the first molecular tether identified in humans, which mediates the contact between these two important cell compartments." The study showed that a protein at the peroxisomes called ACBD5 directly interacts with a protein at the ER, called VAPB. This interaction links both organelles together and allows transfer of lipids between them. When the interaction between VAPB and ACBD5 is lost, the ER and peroxisomes can no longer interact and this lipid transfer appears to be prevented. The researchers are working with experts from the Academic Medical Center in Amsterdam, where a patient with an ACBD5 deficiency has been identified and linked to a peroxisomal defect.
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