mTOR and Beclin1: Two key autophagy‐related molecules and their roles in myocardial ischemia/reperfusion injury

Abstract

Autophagy is the general term of lysosomal degradation of substances in cells, which is considered the key to maintaining the normal structure and function of the heart. It also has a correlation with several heart diseases, in particular, myocardial ischemia/reperfusion (I/R) injury. At the stage of myocardial ischemia, autophagy degrades nonfunctional cytoplasmic proteins providing the critical nutrients for the critical life activities, thereby suppressing cell apoptosis and necrosis. However, autophagy is likely to affect the heart negatively in the reperfusion stage. Mammalian target of rapamycin (mTOR) and Beclin1 are two vital autophagy‐related molecules in myocardial I/R injury playing significant roles in different stages. In the ischemia stage, mTOR plays its roles through AMPK/mTOR and phosphoinositide 3‐kinase/Akt/mTOR pathway, whereas Beclin1 plays its roles through its upregulation in the reperfusion stage. A possible interaction between mTOR and Beclin1 has been reported recently, and further studies need to be done to find the underlying interaction between the two molecules in myocardial I/R injury

Phosphatase and Tensin Homolog (PTEN) of Japanese Flounder—Its Regulation by miRNA and Role in Autophagy, Apoptosis and Pathogen Infection

“…To date, at least 41 ATG proteins have been identified, of which, ATG5 is indispensable for modulating the process of autophagy [ 69 , 70 ]. Beclin 1 is a mammalian ATG6 and functions as a core component of the beclin 1-VPS34 Class III PI3K complex, which serves as a platform for the recruitment of other autophagy proteins during autophagosome biogenesis [ 71 , 72 , 73 ]. The initiation of autophagy is regulated by Class I and Class III PI3K [ 73 ].…”

“…Beclin 1 is a mammalian ATG6 and functions as a core component of the beclin 1-VPS34 Class III PI3K complex, which serves as a platform for the recruitment of other autophagy proteins during autophagosome biogenesis [ 71 , 72 , 73 ]. The initiation of autophagy is regulated by Class I and Class III PI3K [ 73 ]. Class I PI3K inhibits autophagy indirectly via AKT and mTOR, while Class III PI3K directly promotes autophagy through interaction with beclin 1 [ 73 , 74 ].…”

P2X7R-mediated Autophagic Impairment Contributes to Central Sensitization in a chronic Migraine Model with Recurrent Nitroglycerin Stimulation in Mice

“…The activated autophagy usually causes a decrease in p62, while the inhibited autophagy leads to a complete opposite effect [59,63]. In addition, beclin1 is also a key protein re ecting the autophagy activity [59,64]. Therefore, we detected the expression of autophagy-related proteins, including LC3-II, beclin1 and p62, to evaluate the level of autophagic ux in the CM model.…”

Long non‑coding RNA NEAT1 modulates hypoxia/reoxygenation‑induced cardiomyocyte injury via targeting microRNA‑520a

“…It is a type of programmed cell death that contributes to cardiac diseases, including myocardial infarction, heart failure and I/R injury. Cardiomyocyte apoptosis was notably increased in the ischemic hearts in recent studies and subsequently lead to continuous cardiomyocyte loss (14). Several studies have demonstrated that inhibiting apoptosis of cardiomyocytes protected against I/R injury and improved cardiac dysfunction significantly (15,16).…”