Josie A Silvaroli, Bijay Bisunke, Ji Young Kim, Amanda Stayton, Laura A Jayne, Shirely A Martinez, Christopher Nguyen, Prisha S Patel, Thitinee Vanichapol, Vivek Verma, Juheb Akhter, Subhashini Bolisetty, Sethu M Madhavan, Cem Kuscu, Christopher C Coss, Diana Zepeda-Orozco, Samir V Parikh, Anjali A Satoskar, Alan J Davidson, James D Eason, Hazel H Szeto, Navjot Singh Pabla, Amandeep Bajwa
BACKGROUND: The synthetic tetra-peptide SS-31 shows promise in alleviating mitochondrial dysfunction associated with common diseases. However, the precise pharmacological basis of its mitoprotective effects remains unknown. METHODS: To uncover the biological targets of SS-31, we performed a genome-scale CRISPR screen in HK-2 cells, a cell culture model where SS-31 mitigates cisplatin-associated cell death and mitochondrial dysfunction. The identified hit candidate gene was functionally validated using knockout cell lines, siRNA mediated downregulation, and tubular epithelial specific conditional knockout mice...
March 26, 2024: Journal of the American Society of Nephrology: JASN