RETRACTED: Molecular Perspectives of Mitophagy in Myocardial Stress: Pathophysiology and Therapeutic Targets

Abstract

A variety of complex risk factors and pathological mechanisms contribute to myocardial stress, which ultimately promotes the development of cardiovascular diseases, including acute cardiac insufficiency, myocardial ischemia, myocardial infarction, high-glycemic myocardial injury, and acute alcoholic cardiotoxicity. Myocardial stress is characterized by abnormal metabolism, excessive reactive oxygen species production, an insufficient energy supply, endoplasmic reticulum stress, mitochondrial damage, and apoptosis. Mitochondria, the main organelles contributing to the energy supply of cardiomyocytes, are key determinants of cell survival and death. Mitophagy is important for cardiomyocyte function and metabolism because it removes damaged and aged mitochondria in a timely manner, thereby maintaining the proper number of normal mitochondria. In this review, we first introduce the general characteristics and regulatory mechanisms of mitophagy. We then describe the three classic mitophagy regulatory pathways and their involvement in myocardial stress. Finally, we discuss the two completely opposite effects of mitophagy on the fate of cardiomyocytes. Our summary of the molecular pathways underlying mitophagy in myocardial stress may provide therapeutic targets for myocardial protection interventions.

Transcriptomic and Lipidomic Mapping of Macrophages in the Hub of Chronic Beta-Adrenergic-Stimulation Unravels Hypertrophy-, Proliferation-, and Lipid Metabolism-Related Genes as Novel Potential Markers of Early Hypertrophy or Heart Failure

“…Ube2g2 is a putative lipophagy promoting signal [ 82 ] and a regulator of cholesterol efflux [ 81 ]. ECH macrophages were also characterized by an induction of Bnip3 (BCL2/adenovirus E1 B interacting protein 3) involved in mitophagy and potentially exerting cardioprotective survival effects [ 83 ].…”

Mitophagy Regulation Following Myocardial Infarction

“…PINK1 is then able to phosphorylate parkin (an E3 ubiquitin ligase) at Ser65 [ 29 ]. Parkin translocates from the cytoplasm to the surface of the mitochondria [ 16 , 17 , 22 , 30 , 31 , 32 ] and ubiquitinates several proteins from the OMM, such as voltage dependent anion channel 1 (VDAC1) or mitofusin-2 (MFN2). Ubiquitinylated mitochondria are recognized by autophagosomes via some receptors such as P62, optineurin and nuclear dot protein 52 (NDP52) [ 33 , 34 ].…”

“…Mitophagy can also proceed through PINK/parkin independent pathways such as FUN14 domain-containing 1 (FUNDC1), which contains a microtubule-associated proteins 1A/1B light chain 3B (LC3)-interacting region (LIR) domain that facilitates the direct contact with LC3 on autophagosomes [ 17 , 30 , 31 , 40 ]. Under normoxic conditions, FUNDC1 has to be phosphorylated at Tyr-18 by Src kinase and at Ser-13 by casein kinase 2 α (CK2α), which inhibits its interaction with LC3 and prevents mitophagy [ 40 ].…”

“…There are three types of autophagy-microautophagy, chaperone-mediated autophagy (CMA) and macroautophagy (called autophagy in this review). Mitophagy, historically described in Parkinson’s disease, mediates the selective elimination of damaged or dysfunctional mitochondria identified by a decreased mitochondrial membrane potential, a metabolic stress or an accumulation of unfolded proteins [ 14 , 15 , 16 , 17 , 18 , 19 ]. Dysfunctional mitochondria are then degraded by the classical autophagy process.…”

Overexpression of NAF-1 ameliorates Ischemic Stroke in rats by inhibiting PINK1/Parkin-mediated mitophagy

“…Reducing mitochondrial damage is essential in IS [7,8]. Mitophagy is a selective process of autophagy that removes dysfunctional or redundant mitochondria [9]. With moderate mitophagy, nerve cell damage can be reduced [10].…”