Lipid transport is essential to life
Every cell in our body is surrounded by a membrane – a thin, flexible shell mainly consisting of lipids. These lipids have to be transported through both sides of the membrane, a task performed by specialized lipid transport proteins. ”This transport is essential for many vital functions, including the formation and maintenance of cellular membranes, supplying mitochondria with lipids, and transmitting signals during programmed cell death,” explains Veit.
Previously, lipid transporters were mainly examined using ensemble measurements, in which millions of proteins are analyzed at the same time. However, such methods only provide average values and cannot distinguish between individual proteins; individual characteristics and behaviors remain unclear. The international research team was able to overcome this limitation. By using highly sensitive imaging technology as part of this high-throughput method, the researchers were able, for the first time, to precisely measure how quickly an individual protein transports the lipids through the membrane.
Not all proteins act in the same way
The new method was applied to the protein VDAC1. This protein plays a key role in supplying mitochondria with lipids and is only active when two protein molecules assemble into a dimer. “The tests have shown that the individual VDAC1 proteins do not behave identically at all,” says Günther-Pomorski. “While some dimers transported thousands of lipids per second, others were much slower or were even entirely inactive.” This previously unknown variability was not discovered in past ensemble experiments, but can be explained by differences in the manner by which VDAC1 proteins form pairs. Only specific spatial configurations offer a suitable surface for efficient lipid transport, as also confirmed by computer simulations.
Flexible method
The new platform is unique because it is not limited to this one protein and can be used flexibly. A range of proteins that are involved in various biological processes can be examined in the future. Furthermore, the method allows the selective analysis of how different factors influence transport activity. These include various lipid compositions of the membrane or cofactors like special ions.
“A deeper understanding of the functionality of lipid transporters could, in the long term, open up new paths in researching illnesses related to mitochondrial dysfunctions, blood diseases, or disrupted cell death processes,” explains Veit. “Perhaps lipid transporters could even serve as new drug targets.”
Nature Structural & Molecular Biology
Experimental study
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