Threats to mitochondrial respiration in brown fat

The mitochondria are the hidden driver behind the cells that help all parts of the body function as a singular, comprehensive system. Brown fat, which regulates body temperature and total body fat, requires the metabolic mitochondria to burn energy in order to function properly. However, like any other part of the body, certain proteins can undermine this necessary step in the mitochondria’s function. A recent study identifies a metabolic process that can dysregulate that function.

William Sivitz, MD, Emeritus Professor in Endocrinology and Metabolism; Liping Yu, PhD, Adjunct Professor of Biochemistry; and Brian Fink, BS, published a study examining mitochondrial function in brown fat, heart, and skeletal muscle in the Federation of American Society for Experimental Biology (FASEB) Journal.

The study, “Modulation of complex II-energized respiration in muscle, heart and brown adipose mitochondria by oxaloacetate, and complex I electron flow,” tracks the impact of oxaloacetate, a key metabolite in mitochondria, and uncoupling protein-1 (UCP1) on the regulation of mitochondrial respiration in brown fat.

From their research, the investigators found that under certain conditions, UCP1, by decreasing the electrical charge on mitochondria, increases the production of oxaloacetate, impeding the rate at which the mitochondria burn energy. The investigators also examined molecular pathways within mitochondria that affect oxaloacetate production and, therefore, respiration.

With less respiration powering the mitochondria and less cell function in brown fat, fat stores become excessive. The researchers’ study suggests a new origin of diabetes and therefore also opens the gates for new therapeutic treatments. Although their examination focused on isolated mitochondria, “it is difficult not to suspect consequences at the cellular, tissue, and even whole-body level,” Sivitz said. “While future effort will be needed to sort this out, our current work does provide impetus in this direction.”

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