Cytochrome c is a protein found in the mitochondria of eukaryotic cells. It serves a dual purpose: acting as a crucial component in cellular energy production and initiating programmed cell death. Located in the intermembrane space, it is loosely associated with the inner mitochondrial membrane. Cytochrome c is a hemeprotein, containing a heme group with a central iron atom fundamental to its ability to transfer electrons.
The Electron Carrying Capacity
Cytochrome c is capable of carrying exactly one electron at a time. This singular capacity is determined by the chemical properties of the iron atom at the center of its prosthetic heme group. The iron atom functions as the active site for electron transfer, cycling between two specific oxidation states.
When Cytochrome c accepts an electron, the iron atom is reduced from its ferric state (\(Fe^{3+}\)) to its ferrous state (\(Fe^{2+}\)). This change signifies that the protein is now carrying the electron. Once the electron is shuttled to its next destination, the iron atom is oxidized back to the \(Fe^{3+}\) state, freeing it to accept another electron.
This one-electron transfer mechanism is an inherent property of the heme group’s structure. The iron atom can only stabilize the gain or loss of a single charge at a time. This specialized function allows for the precise, sequential movement of electrons necessary for the efficient generation of cellular energy. The reversible switch between the \(Fe^{3+}\) and \(Fe^{2+}\) states enables Cytochrome c to participate in the rapid oxidation-reduction reactions of the respiratory chain.
Function within the Electron Transport Chain
The single electron that Cytochrome c carries is transferred within the Electron Transport Chain (ETC), a series of protein complexes embedded in the inner mitochondrial membrane. The protein acts as a mobile shuttle, operating between Complex III and Complex IV. Its high water-solubility allows it to rapidly diffuse through the intermembrane space to bridge these two large complexes.
Cytochrome c receives its electron from Complex III, also known as the Cytochrome \(bc_1\) complex. This transfer reduces the iron atom in Cytochrome c, completing the first step of the shuttle. Once reduced, the protein detaches from Complex III and moves towards Complex IV, which is also called Cytochrome c oxidase.
The reduced Cytochrome c binds to Complex IV and donates its electron, returning the iron atom to its oxidized state. This electron movement is coupled with the pumping of protons (\(H^+\)) from the mitochondrial matrix into the intermembrane space by Complexes III and IV. The generation of this proton gradient across the inner membrane is the primary purpose of the ETC.
The potential energy stored in this electrochemical gradient is subsequently used by ATP synthase to create adenosine triphosphate (ATP). The continuous shuttling action of Cytochrome c ensures the steady flow of electrons to Complex IV. Complex IV ultimately transfers these electrons to molecular oxygen to form water, which is the culmination of the ETC.
The Role in Programmed Cell Death
Beyond its role in energy production, Cytochrome c initiates programmed cell death, a process known as apoptosis. Under normal conditions, Cytochrome c is confined to the mitochondrial intermembrane space.
When a cell receives signals indicating severe damage or the need for self-elimination, the outer mitochondrial membrane becomes permeable. This causes Cytochrome c to be released from the mitochondria into the surrounding cellular fluid, the cytosol. Once in the cytosol, Cytochrome c no longer participates in the Electron Transport Chain.
Its presence in the cytosol signals the cell to dismantle itself in a controlled manner. Cytochrome c binds to the protein Apoptotic Protease Activating Factor 1 (Apaf-1), leading to the formation of the apoptosome. The apoptosome then recruits and activates initiator caspase enzymes, triggering a cascade of protein-cleaving events. This caspase cascade breaks down the cell’s components, allowing for the safe removal of the dying cell without causing inflammation.