Subsarcolemmal and Intermyofibrillar Mitocondria Metabolism and Dynamics in Rat Heart Aging

The mitochondria are the power plant providing energy for cell survival. The homeostasis of the mitochondrial function is critical, particularly in the heart, in which mitochondria represent the 30% of the muscle mass. In this organ, the stability of their metabolism and mitochondrial dynamic, become fundamental in the diseases onset and in the control of the aging process. This study is based on proteomic and immunoblotting analysis. Intermyofibrillar (IMF), providing energy to muscle fibers, and subsarcolemmal (SS) mitochondria, mediating signalling events, were isolated according to their localization in young (6 months), old adult (22 months) and senescent, (30 months) Sprague Dawley rats, by differential centrifugation in a density gradient. The differences in protein expression were monitored by 2D-DIGE coupled with Maldi Tof and ESI MS/MS. In aging, 2D-DIGE analysis indicates few differences in both: the cardiac muscle proteome and IMF mitochondrial proteome, compared to young controls. Concerning SS mitochondria, significant differences are observed in TCA cycle, lipid metabolism, stress response and OXPHOS. Signalling molecules, analysed by western blotting, indicate an unbalance toward mitochondrial fusion compared to mitochondrial fission. It also appears that mito-authophagy is active and accompanied by the modulation of sirtuin signalling, mitochondrial biogenesis and by a decrease of focal adhesion complexes. Moreover CypD, that promotes PTP opening, is increased. The heart in this aging model presents damage at SS mitochondria level whereas cardiac muscle and IMF mitochondrial fraction is spared to preserve heart function.