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.

TFE3 is a member of the MiT family of the bHLH-leucine zipper transcription factor. We previously focused on the role of TFE3 in autophagy and cancer. Recently, an increasing number of studies have revealed that TFE3 plays an important role in metabolic regulation. TFE3 participates in the metabolism of energy in the body by regulating pathways such as glucose and lipid metabolism, mitochondrial metabolism, and autophagy. This review summarizes and discusses the specific regulatory mechanisms of TFE3 in metabolism. We determined both the direct regulation of TFE3 on metabolically active cells, such as hepatocytes and skeletal muscle cells, and the indirect regulation of TFE3 through mitochondrial quality control and the autophagy–lysosome pathway. The role of TFE3 in tumor cell metabolism is also summarized in this review. Understanding the diverse roles of TFE3 in metabolic processes can provide new avenues for the treatment of some metabolism-related disorders.

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Rationale: Mammalian renal proximal tubules can partially regenerate after acute kidney injury (AKI). However, cells participating in the renal proximal tubule regeneration remain to be elucidated. Wilms' tumor 1 (WT1) expresses in a subtype of glomeruli parietal epithelial cells (PECs) in adult kidneys, it remains unclear whether these WT1 + PECs play a role in renal regeneration/repair after AKI. Methods: Ischemia-reperfusion injury (IRI) mouse model was used to investigate the expression pattern of WT1 in the kidney after severe AKI. Conditional deletion of WT1 gene mice were generated using Pax8 CreERT2 and WT1 fl/fl mice to examine the function of WT1. Then, genetic cell lineage tracing and single-cell RNA sequencing were performed to illustrate that WT1 + PECs develop into WT1 + proximal tubular epithelial cells (PTECs). Furthermore, in vitro clonogenicity, direct differentiation analysis and in vivo transplantation were used to reveal the stem cell-like properties of these WT1 + PECs. Results: The expression of WT1 protein in PECs and PTECs was increased after severe AKI. Conditional deletion of WT1 gene in PTECs and PECs aggravated renal tubular injury after severe AKI. WT1 + PECs develop into WT1 + PTECs via the transient scattered tubular cell stage, and these WT1 + PECs possess specific stem cell-like properties. Conclusions: We discovered a group of WT1 + PECs that promote renal proximal tubule regeneration/repair after severe AKI, and the expression of WT1 in PECs and PTECs is essential for renal proximal tubule regeneration after severe kidney injury.

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