Cytochrome c

Cytochrome c (Cyt c) is a small, soluble heme protein associated with the inner mitochondrial membrane. In the electron transport chain, cytochrome c transfers electrons from Complex III (the cytochrome bc1 complex) to Complex IV (cytochrome c oxidase). It is also a crucial player in apoptosis: if released from mitochondria into the cytosol, cytochrome c helps activate caspases and triggers programmed cell death.

• Within the ETC, cytochrome c carries one electron at a time via its heme group (the iron atom in heme cycles between Fe-- and Fe-- as it accepts and donates electrons). This single-electron transfer is why two cytochrome c molecules are needed to carry the 2 electrons from each molecule of ubiquinol (QH2) through Complex III to Complex IV.
• Cytochrome c is loosely attached on the outer side of the inner mitochondrial membrane (facing the intermembrane space). Because it is not embedded in the membrane, it is one of the components of the ETC that is freely diffusible. This makes it an easily released pro-apoptotic factor: under cellular stress, if the mitochondrial membrane becomes permeable, cytochrome c can leak out into the cytoplasm.
• In the cytoplasm, cytochrome c binding to Apaf-1 (apoptotic protease activating factor-1) and procaspase-9 forms the apoptosome, leading to activation of caspase-9 and then caspase-3. Therefore, a question about the mitochondrial pathway of apoptosis (intrinsic apoptosis) often involves cytochrome c release as a key step.

• Electron transport role: A common question is identifying electron carriers. For example, 'Which electron carrier transfers electrons between Complex III and IV of the mitochondria-' The answer is cytochrome c. It-s unique because it-s a small protein that is not anchored in the membrane, unlike the other ETC complexes.
• Apoptosis clue: If a question describes events in apoptosis such as mitochondrial outer membrane permeabilization or asks 'what mitochondrial protein directly activates the executioner caspases-', the answer is cytochrome c (once in the cytosol, it initiates the cascade leading to cell death).
• Name confusion trap: Don-t confuse cytochrome c with cytochrome c oxidase. Cytochrome c oxidase is Complex IV (an enzyme complex that receives electrons from cytochrome c and uses them to reduce oxygen). Cytochrome c itself is the mobile carrier. If a question mentions inhibition by cyanide affecting cytochrome c oxidase, remember that blocks the ETC at Complex IV, causing cytochrome c to remain reduced and halt further electron transfer.