Empagliflozin attenuates cardiac microvascular ischemia/reperfusion through activating the AMPKα1/ULK1/FUNDC1/mitophagy pathway.

Mitophagy preserves microvascular structure and function during myocardial ischemia/reperfusion (I/R) injury. Empagliflozin, an anti-diabetes drug, may also protect mitochondria. We explored whether empagliflozin could reduce cardiac microvascular I/R injury by enhancing mitophagy.

Molecular mechanisms of coronary microvascular endothelial dysfunction in diabetes mellitus: focus on mitochondrial quality surveillance.

Coronary microvascular endothelial dysfunction is both a culprit and a victim of diabetes, and can accelerate diabetes-related microvascular and macrovascular complications by promoting vasoconstrictive, pro-inflammatory and pro-thrombotic responses. Perturbed mitochondrial function induces oxidative stress, disrupts metabolism and activates apoptosis in endothelial cells, thus exacerbating the progression of coronary microvascular complications in diabetes. The mitochondrial quality surveillance (MQS) system responds to stress by altering mitochondrial metabolism, dynamics (fission and fusion), mitophagy and biogenesis.

FUNDC1 activates the mitochondrial unfolded protein response to preserve mitochondrial quality control in cardiac ischemia/reperfusion injury.

The mitochondrial unfolded protein response (UPR) is an adaptive transcriptional response involving the activation of proteases, chaperones, and antioxidant enzymes and serves to degrade abnormal or unfolded proteins and restore mitochondrial function. Although the cardioprotective action of the UPR has been verified in myocardial ischemia/reperfusion (I/R) injuries, the upstream signals involved remain unclear. Here, we explored the regulatory mechanisms underlying UPR in the reperfused mouse heart.

Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury.

Mitochondrial dysfunction is a fundamental challenge in septic cardiomyopathy. Mitophagy and the mitochondrial unfolded protein response (UPR) are the predominant stress-responsive and protective mechanisms involved in repairing damaged mitochondria. Although mitochondrial homeostasis requires the coordinated actions of mitophagy and UPR, their molecular basis and interactive actions are poorly understood in sepsis-induced myocardial injury.