Rapid and selective generation of H2S within mitochondria protects against cardiac ischemia-reperfusion injury

• DOI: 10.1016/j.redox.2022.102429
• Publication Date: 2022-08-05T03:47:28Z
• Authors: Jan Lj. Miljkovic; Nils Burger; Justyna M. Gawel; John F. Mulvey; Abigail A.I. Norman; Takanori Nishimura; Yoshiyuki Tsujihata; Angela Logan; Olga Sauchanka; Stuart T. Caldwell; Jordan L. Morris; Tracy A. Prime; Stefan Warrington; Julien Prudent; Georgina R. Bates; Dunja Aksentijević; Hiran A. Prag; Andrew M. James; Thomas Krieg; Richard C. Hartley; Michael P. Murphy
• Keywords: Medicine (General); R5-920; QH301-705.5; Hydrogen sulfide donors; Ischemia-reperfusion injury; Biology (General); Reverse electron transport (RET); Mitochondria targeting; Research Paper; Mitochondria; 3. Good health

Mitochondria-targeted H2S donors are thought to protect against acute ischemia-reperfusion (IR) injury by releasing that decreases oxidative damage. However, the rate of release current is too slow be effective upon administration following reperfusion. To overcome this limitation here we develop a mitochondria-targeted agent, MitoPerSulf very rapidly releases within mitochondria. quickly taken up mitochondria, where it reacts with endogenous thiols generate persulfide intermediate H2S. acutely protective cardiac IR in mice, due generation inhibits respiration at cytochrome c oxidase thereby preventing mitochondrial superoxide production lowering membrane potential. agents new class therapy for treatment injury.