2.1.3 Mitochondrial dysfunction
Since the heart constantly needs a large number of energy, mitochondria, as a central energy supply source, play a vital role in maintaining optimal cardiac performance [40]. Mitophagy which functions in regulating energy homeostasis for cells by producing energy in the form of ATP is one of the specialized forms of autophagy that regulates the turnover of damaged and dysfunctional mitochondria [41]. Xu et al . found that SAMM50 sorting and assembly machinery component (Samm50), a key positive regulator of cardiac hypertrophy, promoted cardiac hypertrophy through regulating Pink1-Parkin-mediated mitophagy [42]. Shirakabe et al . found that in transverse aortic constriction (TAC)-treated mouse hearts models, mitophagy and general autophagy were briefly activated and then down-regulated respectively, which ultimately promoted mitochondrial dysfunction and heart failure [43]. Trincado et al. found that in a Parkin -KODrosophila model, disruption of mitophagy lead to mitochondrial dysfunction and accumulation of enlarged mitochondria in heart tubes and dilated cardiomyopathy [44]. Nakayama et al. reported that cardiomyocyte Ca2+ overload as one of the typical characteristics of mitochondrial dysfunction, induced cardiomyocyte cell death via a mitochondrial-dependent necrotic process [45]. These findings suggest that mitophagy induced by mitochondrial dysfunction may play a critical role in the pathogenesis of cardiac hypertrophy.