Paul T Morse, Gonzalo Pérez-Mejías, Junmei Wan, Alice A Turner, Inmaculada Márquez, Hasini A Kalpage, Asmita Vaishnav, Matthew P Zurek, Philipp P Huettemann, Katherine Kim, Tasnim Arroum, Miguel A De la Rosa, Dipanwita Dutta Chowdhury, Icksoo Lee, Joseph S Brunzelle, Thomas H Sanderson, Moh H Malek, David Meierhofer, Brian F P Edwards, Irene Díaz-Moreno, Maik Hüttemann
Skeletal muscle is more resilient to ischemia-reperfusion injury than other organs. Tissue specific post-translational modifications of cytochrome c (Cytc) are involved in ischemia-reperfusion injury by regulating mitochondrial respiration and apoptosis. Here, we describe an acetylation site of Cytc, lysine 39 (K39), which was mapped in ischemic porcine skeletal muscle and removed by sirtuin5 in vitro. Using purified protein and cellular double knockout models, we show that K39 acetylation and acetylmimetic K39Q replacement increases cytochrome c oxidase (COX) activity and ROS scavenging while inhibiting apoptosis via decreased binding to Apaf-1, caspase cleavage and activity, and cardiolipin peroxidase activity...
July 13, 2023: Nature Communications