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Mitochondrial Transfer in Obesity

03/16/2022

Researchers from the Brestoff and Teitelbaum Labs have demonstrated that adipose-tissue resident macrophages acquire mitochondria from adjacent adipocytes using Heparan Sulfate (HS). This process occurs in healthy conditions but is impaired in obesity. Further, they have shown that genetic disruption of mitochondria uptake by macrophages reduces energy expenditure and increases diet-induced obesity in mice, indicating that intercellular mitochondria transfer to macrophages mediates systemic metabolic homeostasis.

Mitochondrial Transfer in Obesity

Obesity is an increasingly common metabolic disease that affects over 40% of adults and 18% of children and adolescents in the United States and is an independent risk factor for the development of many other disorders such as type 2 diabetes, cardiovascular diseases, and cancer.

Head of the group - Professor Jonathan Brestoff commented “Mitochondria are the power plants of cells, and it has long been assumed that they are made in one cell and never leave. We discovered that is not the case and found that fat cells give some of their mitochondria to an immune cell type called macrophages. In obesity, this transferring of mitochondria between cells goes awry, contributing to faster weight gain and worse metabolism. Using a tool called CRISPR, we screened the entire genome and figured out that cells trade mitochondria using a special type of sugar called heparan sulfate, which we think acts as a loading dock for receiving cargo like mitochondria. When we delete heparan sulfates on macrophages, mice get fat. This suggests to us that it is probably good for cells to trade mitochondria with each other. Our team is now trying to figure out how this mysterious and surprising process of mitochondria transfer works because we believe we can harness this biology to treat some human diseases.”

Dr. Wentong Jia, a postdoctoral fellow at the Brestoff lab added “The cell surface expression of heparan sulfate, a glycosaminoglycan required for mitochondria uptake in macrophages, depends on a key glycosyltransferase named EXT1. The 10E4 antibody from AMSBIO has helped us verify that we’ve successfully prevented Heparan Sulfate from being synthesized in cells that lack EXT1.”

“I find it fascinating that cells use heparan sulfates to take up mitochondria,” says Rocky Giwa, a Ph.D. candidate in the Brestoff Lab. “I wonder if there’s a correlation between the amount or composition of heparan sulfates and a cell’s ability to efficiently take up mitochondria from other cells. Since the various HS antibodies have unique specificities, the different clones can help us start to attack that question.”

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Targeting Mitochondria 2022 Congress held on October in Berlin, will dedicate a whole session to Mitochondria Transplantation and Transfer.