Disulfidptosis, Hydrogen Sulfide, and Acute Kidney Injury: Emerging Mechanisms and Therapeutic Intersections
TL;DR
A review of recent findings on the interfaces of disulfidptosis and H2S biology with AKI pathophysiology and potential therapeutic applications aims to incorporate recent findings on the interfaces of disulfidptosis and H2S biology.
Abstract
Acute kidney injury (AKI), a sudden and rapid loss of renal function that is often reversible, encompasses metabolic dysfunction, oxidative stress, inflammation, cytoskeletal collapse, and finally, renal cell death. Besides various types of cell death, like apoptosis, pyroptosis, necroptosis, and ferroptosis, disulfidptosis could be associated with AKI. Disulfidptosis is a novel form of regulated cell death driven by aberrant disulfide stress, which is triggered in glucose-starved cells exhibiting high expression of SLC7A11 (Solute Carrier Family 7 Member 11), which is a cystine/glutamate antiporter. Additionally, disulfidptosis is characterized by a significant disruption in the NADPH/NADP+ ratio and the unusual buildup of disulfides such as cystine (C3H7NO2 S). These alterations ultimately destabilize the F-actin network, leading to cell death. Hydrogen sulfide (H2S), a recognized gasotransmitter, serves as a cytoprotective, redox-regulating, and anti-inflammatory molecule that has attracted interest as a potential regulator of cellular redox equilibrium, actin behavior, and mitochondrial activity in the kidneys. This review aims to incorporate recent findings on the interfaces of disulfidptosis and H2S biology with AKI pathophysiology and potential therapeutic applications.