Work

Subcellular Delivery of Hydrogen Sulfide Using Small Molecule Donors Impacts Organelle Stress

Year: 2022

Type: article

Abstract: Hydrogen sulfide (H 2 S) is an endogenously produced gaseous signaling molecule with important roles in regulating organelle function and stress. Because of its high reactivity, targeted delivery of H 2 S using small molecule H 2 S donors has garnered significant interest to minimize off-target effects. Although mitochondrially targeted H 2 S donors, such as AP39, have been reported previously and exhibit significantly higher potency than nontargeted donors, the expansion of targeted H 2 S delivery to other subcellular organelles remains largely absent. To fill this key unmet need, we report a library of organelle-targeted H 2 S donors that localize H 2 S delivery to specific subcellular organelles, including the Golgi apparatus, lysosome, endoplasmic reticulum, and mitochondria. We measured H 2 S production in vitro from each donor, confirmed the localization of H 2 S delivery using organelle-specific H 2 S responsive fluorescent probes, and demonstrated enhanced potency of these targeted H 2 S donors in providing protection against organelle-specific stress. We anticipate this class of targeted H 2 S donors will enable future studies of subcellular roles of H 2 S and the pathways by which H 2 S alleviates subcellular organelle stress.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.2c07225

Authors: Annie K. Gilbert, Michael D. Pluth

Institution: University of Oregon

Language: English

Topic: Sulfur Compounds in Biology

Subfield: Biochemistry

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Science Foundation, National Institutes of Health, National Institute of General Medical Sciences