Scientists Identify Key Protein from Mitochondria in Energy Regulation

With obesity and obesity-related diseases epidemic in the developed world, a clear understanding of how metabolism is regulated is crucial. One of the key metabolic pathways involves the oxidation of fat. In the current edition of the journal Nature, scientists at the Gladstone Institute of Virology and Immunology report on a new mechanism that governs this pathway and in the process identified a novel potential therapeutic target for controlling fat metabolism.

The target is a protein from the mitochondria, or the "power plants" of every cell that are responsible for processing oxygen and converting substances from the foods we eat into energy for essential cell functions.

"Many mitochondrial proteins undergo a small chemical modification known as acetylation, which varies during feeding and fasting conditions," said Eric Verdin, MD, senior investigator and senior author of the study. "From our previous studies, we knew that the enzyme SIRT3 is involved in removing these modifications, and we speculated that SIRT3 might have a role in regulating metabolism and looked for how it might do this."

To study the enzyme's role in mice, the researchers used mice in which both copies of the gene had been deleted. Interestingly, mice that lost both copies of the SIRT3 gene appeared to be completely normal. However, the investigators then tested the mice under fasting conditions. During fasting, expression of SIRT3 was increased in the liver, an organ that helps maintain the body's energy balance. The livers of mice without SIRT3 had higher levels of fat and triglycerides than normal mice, because the mice could not burn fat...