The pathological role of damaged organelles in renal tubular epithelial cells in the progression of acute kidney injury

Abstract

Acute kidney injury (AKI) is a common clinical condition associated with high morbidity and mortality. The pathogenesis of AKI has not been fully elucidated, with a lack of effective treatment. Renal tubular epithelial cells (TECs) play an important role in AKI, and their damage and repair largely determine the progression and prognosis of AKI. In recent decades, it has been found that the mitochondria, endoplasmic reticulum (ER), lysosomes, and other organelles in TECs are damaged to varying degrees in AKI, and that they can influence each other through various signaling mechanisms that affect the recovery of TECs. However, the association between these multifaceted signaling platforms, particularly between mitochondria and lysosomes during AKI remains unclear. This review summarizes the specific pathophysiological mechanisms of the main TECs organelles in the context of AKI, particularly the potential interactions among them, in order to provide insights into possible novel treatment strategies.

2D-nanomaterials for AKI treatment

“…Emerging evidence has revealed that the key mechanism of AKI is an uncontrolled burst of toxic reactive oxygen species (ROS) in kidneys, which initiates a chain reaction involving cell apoptosis, necrosis, and excessive inflammation ( Wu et al, 2019 ; Zhao et al, 2021a ; Chen et al, 2023 ). As the second energy-consuming organ of the body, renal tubules with a high density of mitochondria become the main site of ROS production and the target of attack during ischemia or hypoxia ( Tian and Liang, 2021 ; Li et al, 2022 ). ROS storms induce severe oxidative stress, causing irreversible damage to DNA, proteins, and other biomolecules, and ultimately leading to tubular cell dysfunction, i.e., a sudden decline in kidney function ( Weng et al, 2021 ; Zhao et al, 2022a ; Huang et al, 2023a ; Wang et al, 2023a ; Su et al, 2023 ).…”

Magnesium Lithospermate B Protects Against Cisplatin-Induced Acute Kidney Injury via Alleviating Mitochondrial Dysfunction

“… 25 , 26 During fission, Drp1 oligomerizes around the mitochondria to form a ring structure that uses the energy generated by GTP hydrolysis to divide the mitochondria. 27 In STZ-induced diabetic mice, the increase in Drp1 expression was accompanied by mitochondrial and cardiac dysfunction. 28 Chen et al indicated that mito-Drp1 is recruited from the cytoplasm to the mitochondria in high glucose-induced podocytes.…”

Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

“…In various types of AKI, harmful substance accumulation in the tubules leads to disrupted renal redox balance by inducing immune cells, endothelial cells, and RTECs to produce large amounts of RONS [ 74 ]. Furthermore, kidney hypoxia from persistent hypoperfusion, I/R, or microcirculatory disturbances causes intracellular mitochondria to produce large amounts of RONS [ 75 ]. Therefore, RONS overproduction is a central mechanism for the induction of oxidative stress, inflammation, adaptive response, and adaptive responses in AKI.…”