SLC25A30 Regulates Mitochondrial Autophagy Through the PINK1/PARKIN Signaling Pathway to Alleviate Sepsis-Associated Acute Kidney Injury

This study aims to investigate the expression of the SLC25 subfamily in sepsis-associated acute kidney injury (SA-AKI) and the role of SLC25A30 in regulating PINK1/PARKIN-mediated mitophagy. Transcriptome sequencing of renal tissues from lipopolysaccharide (LPS)-induced SA-AKI rats at multiple time points revealed time-dependent differential expression of SLC25 genes. At 12 h post-LPS injection (renal injury peak), 11 differentially expressed genes were identified. Intersection with Gene Expression Omnibus datasets and Gene Ontology enrichment highlighted 11 codifferentially expressed genes enriched in mitochondrial transmembrane transport. Notably, SLC25A30 was significantly negatively correlated with KIM-1 ( r = –0.96) and LCN2 ( r = –0.98). SLC25A30 was significantly downregulated in SA-AKI rat renal tissues and LPS-induced HK-2 cells, accompanied by upregulated PINK1/PARKIN, excessive mitophagy (elevated LC3B-II, decreased p62), and increased renal injury markers. SLC25A30 overexpression inhibited PINK1/PARKIN, reversed excessive mitophagy, reduced KIM-1 and LCN2 levels, alleviated mitochondrial dysfunction, enhanced cell viability, and exerted cytoprotective effects. PINK1 knockdown attenuated the regulatory effect of SLC25A30 on excessive mitophagy, indicating a dependence on the PINK1/PARKIN pathway. In conclusion, downregulated SLC25A30 is closely associated with excessive mitophagy in SA-AKI. SLC25A30 overexpression inhibits excessive mitophagy via downregulating the PINK1/PARKIN pathway, improves mitochondrial function, and alleviates HK-2 cell injury, suggesting that SLC25A30 may be a novel molecular target for SA-AKI-targeted therapy.