Critical hubs of renal ischemia-reperfusion injury: endoplasmic reticulum-mitochondria tethering complexes

Abstract

Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process

“…The pathogenic mutation in α-Syn, one kind of PD-related gene, leads to pathological changes in MAMs, decreases its association, and disrupts autophagy [78][79][80][81]. In addition, PINK1induced alterations in MAMs have been observed in renal ischemia-reperfusion (I/R) [82]. It has been demonstrated that the contact between PINK1 and the preautophagic protein Beclin1 could increase MAMs and regulate mitophagy, thereby helping relieve renal I/R injury by regulating 3 Oxidative Medicine and Cellular Longevity mitophagy [83,84].…”

Endoplasmic Reticulum-Mitochondria Contacts: A Potential Therapy Target for Cardiovascular Remodeling-Associated Diseases

“…In 1990, MAMs were interpreted as a point of contact between ER membranes and mitochondria by Vance (1990) . Electron tomography has shown that the ER and mitochondria are connected by tethers (9–16 nm for smooth ER and 19–30 nm for rough ER) ( Simmen and Herrera-Cruz, 2018 ; Zhao et al, 2020 ). Further studies showed that MAMs are formed when the ER is close to the mitochondria by approximately 20 nm on 20% of the mitochondrial surface ( Csordas et al, 2006 ).…”

“…Myocardial ischemia/reperfusion (I/R) injury is defined as a pathophysiological phenomenon in which the structural damage and dysfunction of cells or tissues are instead progressively aggravated after the ischemic myocardium returns to normal perfusion ( Zhao et al, 2020 ). Studies on the mechanism of myocardial I/R injury have been conducted for decades, and it is mainly considered to be related to cellular redox imbalance, calcium overload, ER stress, mitochondrial injury, energy depletion, and programmed cell death ( Toth et al, 2007 ; Consolini et al, 2017 ; Gong et al, 2021 ).…”

CD44 Receptor-Targeted and Reactive Oxygen Species-Responsive H2S Donor Micelles Based on Hyaluronic Acid for the Therapy of Renal Ischemia/Reperfusion Injury

“…ROS is a series of chemically reactive metabolites, including ClO – , H 2 O 2 , O 2– , and so on. In ischemic injury, ROS generates oxidative stress and regulates certain signaling pathways, such as NF-κB, caspase-3, and p53 . The abundance of ROS damages human cells severely by disrupting organelles, cell membranes, and nuclear DNA if not eliminated by antioxidants .…”

“…At present, there are many ways for renal drug delivery. Cerium oxide nanoparticles, nanopatricles, , gold particles, SiO 2 nanospheres, and lipid calcium phosphate gel have been studied for improving hydrophobic drug solubility, raising accurate targeting, enhancing precision, declining adverse drug reactions, and multiple other uses. In this study, novel multifunctional nanoparticles were designed to treat IR injury, which had a critical treatment effect and superior potential.…”