Researchers Discover that Cells Contain Mitochondria Specialized to Build Fats
A new definition of mitochondria has emerged due to research conducted at BUSM. In the past mitochondria have been seen as the cellular organelle where sugars and fats are oxidized to generate energy. Now, because of a study done by researchers including BUSM MD/PhD candidate Ilan Benador, the study’s first author, we now know that not all mitochondria fit this definition.
According to the findings published in Cell Metabolism, researchers found that within each cell a group of specialized mitochondria can be found attached to fat droplets.
“We first noticed this when looking at the cells under the microscope,” said Mr. Benador. “We saw that mitochondria surrounding the lipid droplet had different size and shape and didn’t move around as much as rest of the mitochondria in the cell,” he added.
The team then developed a method to separate these mitochondria from the rest of the cell components. “Our method took advantage of the basic principle that fat floats over water,” said BUSM Graduate Kiana Mahdaviani, the study’s second author. The team discovered that a specialized subgroup of mitochondria remained attached to the fat droplets, which could be separated from the rest of the cell mitochondria. “This really changes how we look at previous mitochondrial research, which routinely discarded the fat droplets,” said Mr. Benador.
Once isolated, the team found that lipid droplet-associated mitochondria have distinct biochemistry and metabolism. To better understand how these mitochondria work in the body, the team studied brown fat, a type of fat tissue that can activate fat oxidizing to generate heat. “We expected to have lot more lipid droplet-associated mitochondria in activated brown fat but saw exactly the opposite,” said Mr. Benador. This suggested the fat droplet-associated mitochondria are not specialized for fat oxidation. In fact, manipulation of brown fat cells demonstrated that fat-droplet associated mitochondria promote fat droplet expansion. “We are very excited to see how this discovery will improve our understanding and treatment of obesity and other metabolic disorders,” said Mr. Benador. The team is now working towards identifying drug candidates that disrupt mitochondrial interaction with fat droplets.
The two corresponding authors of the study, Drs. Orian Shirihai and Marc Liesa were BUSM Department of Medicine faculty for the majority of the study. The study’s other authors are: BUSM PhD Graduate Kiana Mahdaviani and BUSM Professor Barbara Corkey ; Anton Peterski, Essam Assali, Rebeca Asin-Perez, Michael Shum, William Barshop and James Wohlschlegel, all of UCLA; Jakob Wilkstrom of the Karolinska Institutet; Marcus Oliviera of Universidade Federal do Rio de Janiero; Saviero Cinti of the University of Ancona; and Carole Sztalryd of the University of Maryland Baltimore County.
Funding for the study and the researchers involved was provided by the Boston University T32 Training Program in Metabolism, Endocrinology and Obesity; the National Institutes of Health; a UCSD/UCLA Diabetes Research Center grant; and the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico.