Spatial proteomics reveals multiple mechanisms of mitochondrial damage in renal tubules during sepsis-induced acute kidney injury.

Sepsis-associated acute kidney injury (SA-AKI) is a common critical illness in clinical practice with a high mortality rate and is closely related to the clinical outcomes of critically ill patients. The microstructure of the kidney is highly complex, and targeted proteomic analysis of renal tubules can help us study the pathological process of SA-AKI. In the present study, we accurately separated, collected, and compared the proximal tubular structures of mice with SA-AKI and healthy mice using spatial proteomics and mass spectrometry (MS) techniques. We identified 126 upregulated and 105 downregulated proteins, indicating that damage to the SA-AKI process occurred primarily in the mitochondria. The functions of significantly differentially expressed proteins such as SCL34A1 and HO-1 were validated in the HK-2 cell line, and several pathways of mitochondrial dysfunction were observed: 1. Reduced phosphate led to oxidative phosphorylation disorders. 2. The Fenton reaction damaged the mitochondria, and 3. Excessive mitochondrial autophagy provided a novel potential target for the treatment of septic kidney injury. The MS proteomic data were deposited in the ProteomeXchange Alliance (https://proteomecentral.proteomexchange.org) using the iProX partner repository with the dataset identifier IPX0008335000.