Therapeutic Approaches Involving Mitochondria in the Treatment of Acute Kidney Injury.

Review article synthesizing preclinical and clinical evidence on mitochondrial dysfunction in AKI

“This review synthesizes current mitochondrial-directed approaches for AKI, with a particular emphasis on the mechanistic role of PLSCR3 in maintaining mitochondrial homeostasis and injury responses.”

Human renal proximal tubule cells, mice, rats, and porcine models

“Using a genome-wide CRISPR-Cas9 screen in human renal proximal tubule cells under cisplatin stress, we found that PLSCR3 was the top gene required for SS-31’s cytoprotective effect.”

PLSCR3 is identified as a critical mediator required for the cytoprotective effects of SS-31 in AKI models

“Deletion of PLSCR3 abolished SS-31’s benefit without affecting baseline injury sensitivity.”

SS-31 binds to the N-terminal domain of PLSCR3 to enhance scramblase activity and stabilize mitochondrial ultrastructure

“SS-31 binds the N-terminal domain of PLSCR3, enhancing its scramblase activity and stabilizing inner membrane ultrastructure.”

PLSCR3 expression is upregulated in human AKI biopsies

“Moreover, PLSCR3 is upregulated in human AKI biopsies, supporting its relevance as both a mechanistic biomarker and a therapeutic target.”