PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation

Abstract

Contrast-induced acute kidney injury (CI-AKI) occurs in more than 30% of patients after intravenous iodinated contrast media and causes serious complications, including renal failure and mortality. Recent research has demonstrated that routine antioxidant and alkaline therapy failed to show benefits in CI-AKI patients with high risk for renal complications. Mitophagy is a mechanism of selective autophagy, which controls mitochondrial quality and mitochondrial reactive oxygen species (ROS) through degradation of damaged mitochondria. The role of mitophagy and its regulation of apoptosis in CI-AKI are poorly understood. In this study, we demonstrated that mitophagy was induced in renal tubular epithelial cells (RTECs) during CI-AKI, both in vivo and in vitro . Meanwhile, contrast media–induced mitophagy was abolished when silencing PINK1 or PARK2 (Parkin), indicating a dominant role of the PINK1-Parkin pathway in mitophagy. Moreover, mitochondrial damage, mitochondrial ROS, RTEC apoptosis, and renal injury under contrast exposure were more severe in PINK1- or PARK2-deficient cells and mice than in wild-type groups. Functionally, PINK1-Parkin–mediated mitophagy prevented RTEC apoptosis and tissue damage in CI-AKI through reducing mitochondrial ROS and subsequent NLRP3 inflammasome activation. These results demonstrated that PINK1-Parkin–mediated mitophagy played a protective role in CI-AKI by reducing NLRP3 inflammasome activation.

Augmenter of Liver Regeneration Protects Renal Tubular Epithelial Cells From Ischemia-Reperfusion Injury by Promoting PINK1/Parkin-Mediated Mitophagy

“…Many studies have reported that PINK1/Parkin signaling controls the selective degradation of dysfunctional mitochondria by mitophagy in acute kidney disease (Zhao et al, 2017;Tang et al, 2018;Lin et al, 2019). In healthy mitochondria, PINK1 is constitutively inserted into the mitochondria inner membrane and rapidly degraded by proteolysis to keep a low level of expression.…”

“…In kidney disease, the PINK1/Parkin pathway was reported to play a dominant role in mitophagy (Lin et al, 2019). In this study, an activation of the PINK1/Parkin pathway at the time point of I6R12 was measured using immunofluorescence and immunoblot analysis.…”

P53 and Parkin co-regulate mitophagy in bone marrow mesenchymal stem cells to promote the repair of early steroid-induced osteonecrosis of the femoral head

“…Could enhancing mitophagy to clear these accumulated mitochondria effectively resist BMSCs stress-induced apoptosis and senescence? Mitophagy mediated by the PINK1-Parkin pathway is the most important way to clear damaged mitochondria 37,38 ; mitochondrial translocation of Parkin is very important to mitophagy 39 , and therefore increasing the content of Parkin in cells can be expected to increase mitochondrial translocation of Parkin and thus enhance mitophagy. Therefore, we used lentiviral vector-encoded Parkinenhanced green fluorescent protein (Lv-Parkin-EGFP) to transfect BMSCs.…”

Acetylbritannilactone attenuates contrast-induced acute kidney injury through its anti-pyroptosis effects

“…In recent years, vascular administration of iodinated contrast media (CM) has been widely used in patients undergoing diagnostic cardiac angiography and percutaneous coronary intervention [1]. Contrast-induced acute kidney injury (CI-AKI) occurs in more than 5-15% of patients after percutaneous coronary intervention via CM [2], which is associated with risk factors, such as advanced age, diabetes, and hypertension [3]. CI-AKI is the third most common cause of acute renal failure in hospitalized patients after hypoperfusion and nephrotoxic drugs [4].…”