Upstream stimulatory factor 2 protects cardiomyocytes by regulating
mitochondrial homeostasis
Abstract
Myocardial ischemia and hypoxia are one of the main causes of heart
failure, and cardiomyocyte apoptosis induced by mitochondrial injury is
the basis of poor heart remodeling and heart failure. Upstream
stimulatory factor 2 (USF2), a transcription factor involved in multiple
cellular processes, has recently been identified as having an active
role in mitochondrial function and energy homeostasis; however, the role
of USF2 in cardiovascular disease has not been reported. In this study,
we demonstrated that the expression of USF2 protein can be degraded by
the ubiquitin-proteasome pathway when cardiomyocytes are hypoxic, and
the loss of USF2 can lead to mitochondrial dysfunction in
cardiomyocytes, aggravating mitochondrial damage and further promoting
apoptosis.Mechanistically, we also demonstrate that USF2 deficiency
induces mitochondrial autophagy by [regulating](javascript:;) the
AMPK/mTOR signaling pathway.Altogether, this study provides new insights
into the protective role of USF2 in hypoxic cardiomyocyte injury. USF2
may serve as a potential therapeutic target for myocardial hypoxia.