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.