Resonance Raman applications in investigations of cytochrome c oxidase

► Resonance Raman (RR) spectroscopy was applied to cytochrome c oxidase (CcO). ► The fully-oxidized “as-isolated” CcO was revealed to have the Fe―O22 −―Cu center. ► Oxygen activation by CcO in situ in mitochondria could be studied by RR spectroscopy. ► CcO in situ and solubilized CcO shared essentially the same reaction intermediates. ► The oxygenated intermediate in situ decayed much slower than for solubilized CcO.