IDIBAPS researchers discover a new mechanism that allows cells to take advantage of fat excess

IDIBAPS researchers have discovered the mechanism by which two cell organelles, lipid droplets (LDs) and mitochondria, interact to exchange the fatty acids that the LDs contain to mitochondria to produce energy during nutrient starvation. This is achieved thanks to special microtubules, as a kind of highway, on which LDs relocate and move up to the mitochondria. The work has been published in the journal Nature Communications and is led by Dr. Albert Pol, ICREA Professor of the Cell Compartments and Signaling IDIBAPS team and professor in the Faculty of Medicine of the University of Barcelona (UB). The first authors of this paper, made in collaboration with the University of Queensland (Australia) and the University of California (USA), are Dr. Albert Herms and Dr. Marta Bosch, researchers from the IDIBAPS team.

Fats are essential for life, but very toxic in excess. All the cells contain lipid droplets (LDs), organelles that store the fatty acids excess allowing the cell to reduce its toxicity and supplying them when there is an energy requirement. Although its function is well described in adipocytes, the body’s cell subtype specialized in the accumulation of fat, little is known about the role of LDs in the other cells and the mechanism of interaction with other cellular organelles. The knowledge of these mechanisms would be very important since an excessive accumulation of LDs is the cause of diseases associated with obesity, such as type II diabetes, and atherosclerosis, metabolic syndrome and fatty liver disease.

In the study published in Nature Communications, researchers have found that when nutrients are removed from the cells culture media, the distribution pattern of LDs changes from the cell centre, around the nucleus, to the cell periphery -dispersed in the cytoplasm. By delving into the responsible mechanism, they have discovered that a special kind of cytoskeleton microtubules, which organize the three-dimensional structures of cells and take part in transport and cell division, are involved. LDs are relocated and travel through these microtubules, at the end of which are the mitochondria, facilitating the transformation of fatty acids into energy. This mechanism is used by the cell for a fast and efficient production of energy when nutrients are missing.

For all this to happen, the activation of an enzyme called AMPK (AMP-activated protein kinase), which is a cellular energy sensor that helps in the energy balance and calories consumption, is needed. Researchers have shown that AMPK acts simultaneously increasing the mobility of LDs, reorganizing the network of microtubules and activating mitochondria both in normal and starvation conditions.

Many diseases arise from a deficiency in the bioenergetic mechanisms of cells and LDs accumulation in different tissues is associated with several highly prevalent pathologies. This article shows which is the mechanism to mobilize LDs for energy production, both in normal and scarcity conditions. This discovery may deepen the understanding of the causes and treatment of diseases such as diabetes and atherosclerosis: "We have seen that with the administration of a drug such as metformin, one of the most used in the treatment of Type II Diabetes, all processes to mobilize LDs are triggered, allowing fat burning and bending energy production efficiency", explains Dr. Albert Pol, the study coordinator.

Article reference:

AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

Albert Herms, Marta Bosch, Babu J.N. Reddy, Nicole L. Schieber, Alba Fajardo, Celia Rupérez, Andrea Fernández-Vidal, Charles Ferguson, Carles Rentero, Francesc Tebar, Carlos Enrich, Robert G. Parton, Steven P. Gross, Albert Pol

Nature Communications 6, Article number: 7176 doi:10.1038/ncomms8176