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Show THE UNIVERSITY OF UTAH HEALTH SCIENCES LEAP PROGRAM AUTOPHAGY REGULATES MITOCHONDRIAL BIOGENESIS IN THE HEART Fermin Suarez (Zhonggang Li, Dale Abel) Department of H u m a n Genetics University of Utah Background The process of autophagy occurs in the heart and the rate of autophagy increases in the heart during stress such as exercise. Autophagy in the heart may lead to the remodeling of mitochondria, which can lead to improved heart function. Methods We had two different types of mice: one set of mice had unaltered genes (WT mice) while the other type of mice had the beclin 1 gene knocked down (BCN +/- mice). W T and BCN +/- mice underwent an exercise protocol that consisted of one hour running on the treadmill for five days a week for four weeks. At five weeks, the mice were sacrificed and the heart tissues were harvested. The mRNA as well as protein expression were analyzed compared to their sedentary control mice. Results Both exercised W T and BCN+/- mice showed weight loss compared to their sedentary control. Exercise did not show any significance on blood glucose levels and heart weight. Exercise induced higher autophagy level in W T mice but not in BCN+/- mice. There was a slight increase in the left ventricular posterior wall thickness in W T mice while the BCN+/- mice exhibited no growth. Moreover, after 4-weeks of exercise, the W T mice had increased mitochondrial DNA copy number as well as higher levels of mitochondrial biogenesis (TFAM, NRF-1, NRF-2 m R N A expression), which were blunted in BCN+/- mice. Conclusions The W T mice showed to have more mitochondrial biogenesis than the BCN+/- mice after exercise, which indicated autophagy may be involved in mitochondrial biogenesis. Further research is needed to illustrate the potential mechanism. Fermin Suarez Zhonggang Li Dale Abel |