8dzl
From Proteopedia
Structure of the K39Q mutant of rat somatic Cytochrome c at 1.36A
Structural highlights
FunctionCYC_RAT Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain. Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases (By similarity). Publication Abstract from PubMedSkeletal 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. These results are discussed with X-ray crystallography structures of K39 acetylated (1.50 A) and acetylmimetic K39Q Cytc (1.36 A) and NMR dynamics. We propose that K39 acetylation is an adaptive response that controls electron transport chain flux, allowing skeletal muscle to meet heightened energy demand while simultaneously providing the tissue with robust resilience to ischemia-reperfusion injury. Cytochrome c lysine acetylation regulates cellular respiration and cell death in ischemic skeletal muscle.,Morse PT, Perez-Mejias G, Wan J, Turner AA, Marquez I, Kalpage HA, Vaishnav A, Zurek MP, Huettemann PP, Kim K, Arroum T, De la Rosa MA, Chowdhury DD, Lee I, Brunzelle JS, Sanderson TH, Malek MH, Meierhofer D, Edwards BFP, Diaz-Moreno I, Huttemann M Nat Commun. 2023 Jul 13;14(1):4166. doi: 10.1038/s41467-023-39820-8. PMID:37443314[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
