心肌肥厚是在细胞内外信号综合作用下，出现的以线粒体稳态失衡及其促发的应激损伤、能量代谢障碍、钙离子稳态失调为特征的病理生理过程，也是心力衰竭的前奏。作为线粒体外膜转运酶复合体的重要亚基，Tom70通过识别和协助转运线粒体前体蛋白在维持线粒体稳态中发挥关键作用。最新发现，Tom70是整合外源性肥厚应力和线粒体应激反应的“分子开关”，决定着病理性心肌肥厚的发展。 我们前期发现了核受体RXRα具有抑制和逆转心肌肥厚的保护作用，在此过程中，Tom70蛋白受到RXRα的调节和修复，提示Tom70介导的线粒体稳态矫正可能是RXRα调控心肌肥厚的新机制。在此基础上，本研究将探讨RXRα调控心肌细胞线粒体稳态的效应、分子机制及其对心肌肥厚发展和转归的影响，重点研究Tom70蛋白的介导作用，为心肌肥厚和心力衰竭的预防探寻新的干预靶点。

As the prelude of heart failure, myocardial hypertrophy is a pathophysiological response driven by exterior and interior cellular signaling systems. At the cellular level, cardiomyocyte hypertrophy is characterized by mitochondrial derangement and succeeding oxidative stress, abnormal energy metabolism and perturbations of cellular Ca2+ homeostasis. Being an important receptor of the translocases complex of mitochondrial outer membrane (Tom), Tom70 recognize mitochondrial-targeting sequences on the precursor proteins and transfer these proteins to the central channel, which is critically required for the maintenance of mitochondrial homeostasis. In recent study, it was revealed that Tom70 acts as a molecular switch that orchestrates hypertrophic stresses and mitochondrial responses to determine pathological cardiac hypertrophy. We have found that nuclear receptor RXRα can inhibit and attenuate pressure overload-induced cardiac hypertrophy by modulating and repairing Tom70 receptor, which implies that Tom70-mediated restoration of impaired mitochondrial homeostasis may be the new mechanism for RXRα to modulate cardiac hypertrophy. On the basis of our previous study, we will investigate the corrective action of RXRα on mitochondrial homeostasis and underlying molecular mechanism, especially the critical mediating effect of Tom70, to identify the target for the prevention of cardiac hypertrophy and heart failure.