Respiration triggers heme transfer from cytochrome c peroxidase to catalase in yeast mitochondria

We provide to our knowledge the first in vivo and in vitro evidence for H₂O₂-triggered heme transfer between proteins. Specifically, H₂O₂ binds to and labilizes cytochrome c peroxidase (Ccp1)'s heme by oxidizing the proximal Fe ligand (His175), which activates Ccp1 to transfer its heme to apoCta1, and apoCcp1 subsequently escapes from mitochondria. This sequence of H₂O₂-activated heme labilization, heme transfer between proteins, and protein relocalization defines a previously undefined mechanism of H₂O₂ signaling in cells. In contrast, established H₂O₂ signaling mechanisms are dominated by thiol-based redox changes.