Complex III, also known as the cytochrome bc1 complex, is a large protein complex located within the inner membrane of mitochondria. Mitochondria are often called the “powerhouses” of the cell, and Complex III plays a role in their ability to generate energy. It functions as a component of the electron transport chain, a series of protein complexes that work together to produce cellular energy. This complex is a part of the broader process of oxidative phosphorylation, which is how cells synthesize adenosine triphosphate (ATP), the primary energy currency of the cell.
How Complex III Generates Energy
Complex III functions as a link in the electron transport chain, receiving electrons from a molecule called ubiquinol (QH2). Ubiquinol acts as a mobile carrier, delivering electrons that originated from earlier steps in cellular respiration. Complex III then transfers these electrons to cytochrome c.
As electrons move through Complex III, energy is released, which the complex uses to pump positively charged hydrogen ions, or protons, from the mitochondrial matrix into the intermembrane space. This movement of protons creates a higher concentration of protons in the intermembrane space compared to the matrix. This difference in concentration, along with an electrical charge difference, forms an electrochemical gradient across the inner mitochondrial membrane.
This electrochemical gradient is known as the proton motive force. The potential energy stored in this gradient is harnessed by ATP synthase. Protons flow back into the mitochondrial matrix through ATP synthase, and this flow drives the synthesis of ATP from adenosine diphosphate (ADP) and inorganic phosphate. Complex III’s role in establishing this proton gradient is directly connected to ATP production.
The Unique Q Cycle Mechanism
Complex III employs a unique mechanism known as the Q cycle to efficiently transfer electrons and pump protons. In this cycle, two electrons from ubiquinol (QH2) are handled distinctly.
One electron is transferred to the Rieske iron-sulfur protein. This electron then moves to cytochrome c1, and subsequently to cytochrome c, which carries it to the next complex in the chain. The second electron from the original ubiquinol molecule takes a different path, going through two heme groups within cytochrome b. This electron then reduces a molecule of ubiquinone (Q) back to ubiquinol (QH2).
The Q cycle allows Complex III to utilize both electrons from ubiquinol for proton pumping and electron transfer, enhancing the overall efficiency of the electron transport chain. For every two electrons transferred through Complex III, four protons are pumped from the mitochondrial matrix into the intermembrane space. This mechanism maximizes the contribution to the proton gradient, supporting greater ATP synthesis.
Building Complex III
Complex III is a complex assembly of multiple protein subunits. In higher animals, this complex consists of eleven subunits. Three of these are notable for their involvement in electron transfer: cytochrome b, cytochrome c1, and the Rieske iron-sulfur protein.
Cytochrome b contains two heme groups involved in electron transfer. Cytochrome c1 possesses one c-type heme, participating in electron transport. The Rieske iron-sulfur protein contains a two-iron, two-sulfur cluster, involved in electron transfer.
The assembly of Complex III is a complex process within the cell. This involves the coordinated expression and folding of subunits encoded by both mitochondrial and nuclear DNA, followed by their integration into the inner mitochondrial membrane. Various cellular factors and chaperones ensure the correct assembly and stability of this multi-subunit complex for its proper function.
Complex III and Human Health
The proper functioning of Complex III is important for human health, given its role in cellular energy production. When Complex III activity is impaired, it can lead to reduced ATP synthesis. Cells and tissues with high energy demands, such as those in the brain, heart, and muscles, are sensitive to such disruptions.
Dysfunction of Complex III can result in metabolic consequences. Reduced energy availability can affect various physiological processes, leading to impairments in organ function. Issues with energy production can manifest as diverse health problems. Maintaining the integrity and activity of Complex III is important for overall cellular and organismal well-being.