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What Happens When the Body Signals a Need for Energy

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Scientists Discover Molecular Switch That Controls if Fat Is Stored or Burned

Even the smallest errors in lipid metabolism can lead to high cholesterol levels (blood lipid levels), increasing the risk of cardiovascular diseases, obesity, or diabetes.

Our body’s energy production heavily relies on the balance of fat metabolism. Scientists at the University of Basel, Switzerland, have made a groundbreaking discovery—a molecular switch that finely regulates lipid metabolism within our cells. This switch exerts control over the storage and conversion of lipids into energy.

Energy is an indispensable requirement for all living organisms, obtained through various components of our diet. While a portion of this energy is utilized immediately, the excess is stored. Glucose serves as an instantly accessible energy source, while fats are reserved in the form of lipid droplets within our cells.

When the body demands energy from these fat stores, lipids are transported to the mitochondria—the cellular powerhouse. Here, lipids undergo conversion into ATP (adenosine triphosphate), a critical molecule supplying energy to our cells.

Yet, the questions arise: How much energy does our body necessitate from these energy reserves? What proportion of lipids should be transformed into ATP? When should this process commence and conclude? Professor Anne Spang’s research team at the Biozentrum, University of Basel, delved into lipid metabolism in both yeast and human cells.

Their investigations uncovered a remarkable protein named Arf1, functioning as a molecular switch, deftly regulating these processes.

The noteworthy findings have been recently published in “Nature Cell Biology.”

Arf1 protein alters the contact site between lipid droplets and mitochondria, facilitating energy flow

“Arf1 is a familiar protein to us. We already know that it has several functions in the Golgi apparatus, the cell’s sorting station. We have now discovered that Arf1 also plays a role in regulating energy metabolism in the mitochondria,” adds first author Dr. Ludovic Enkler. “Arf1 ensures the transport of lipids from lipid droplets to mitochondria.”

Researchers hypothesize that Arf1 modifies the environment at the contact site between lipid droplets and mitochondria, enabling lipids to penetrate the mitochondria.

When the body signals the need for energy, Arf1 grants passage to lipids into the mitochondria. Once the energy demand is satisfied, the transport ceases.

“Thus, the system only works when the feedback loop of the energy requirements works,” adds Ludovic Enkler.

Disrupted energy flow: Consequences of overactive or absent Arf1

“However, if the Arf1 protein is absent or overactive, the entire system gets out of balance,” remarks Anne Spang. “In both cases, the feedback control between demand and production does not work, leading to insufficient ATP energy supply. Consequently, fatty acids accumulate in lipid droplets.”

The sensitivity and intricate complexity of lipid metabolism become evident when considering various lipid metabolism disorders. Even minor errors in lipid metabolism can lead to elevated blood lipid levels (high cholesterol), heightening the risks of cardiovascular diseases, obesity, and diabetes.

Employing advanced techniques like spatial proteomics, capable of studying all proteins within different cellular structures, the research team strives to identify the specific components involved in the feedback process of Arf1 protein in cells.

Their ultimate objective is to unravel the intricate details of lipid trafficking at the contact sites between lipid droplets and mitochondria.

Source: 10.1038/s41556-023-01180-2

Image Credit: Shutterstock

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