Cellular respiration allows cells to convert the chemical energy stored in nutrient molecules, primarily glucose, into a usable form called adenosine triphosphate (ATP). This process is highly organized and does not happen in a single location. Instead, it is a sequential, multi-stage pathway requiring the precise environment of several distinct cellular compartments to complete the conversion.
Glycolysis: The Starting Point in the Cytosol
The process of cellular respiration begins in the cell’s cytosol, outside the main energy-generating organelle. This initial stage is called glycolysis. Glycolysis involves a ten-step sequence of enzyme-catalyzed reactions that break one six-carbon glucose molecule into two three-carbon molecules of pyruvate. This stage is anaerobic, meaning it does not require oxygen to proceed.
Glycolysis requires an investment of two ATP molecules initially. However, the later steps produce four ATP molecules, yielding a net gain of two ATP per glucose molecule through substrate-level phosphorylation. Glycolysis also produces two molecules of the high-energy electron carrier nicotinamide adenine dinucleotide (NADH). The resulting pyruvate and NADH must then move into the next cellular location to continue the aerobic pathway.
The Mitochondrial Matrix: Linking and Cycling
Following glycolysis, the two pyruvate molecules are actively transported across the mitochondrial membranes into the mitochondrial matrix. The matrix is the gel-like solution that fills the innermost compartment of the mitochondrion and contains the specific enzymes necessary for the next two reaction sets. Pyruvate first undergoes oxidative decarboxylation, a transition step that converts the three-carbon pyruvate into acetyl-coenzyme A (acetyl-CoA). This conversion releases carbon dioxide and generates a molecule of NADH, linking glycolysis to the next major cycle.
The acetyl-CoA then enters the Citric Acid Cycle, also known as the Krebs Cycle, which is a closed loop of eight reactions occurring entirely within the matrix. The primary function of this cycle is to complete the breakdown of the carbon fuel by systematically oxidizing the acetyl-CoA. This process releases all remaining carbon atoms as carbon dioxide. The cycle produces only a small amount of direct energy, equivalent to one ATP or guanosine triphosphate (GTP) per turn. Its most important output is the generation of high-energy carriers: three NADH and one flavin adenine dinucleotide (FADH2) molecules for every turn. These molecules carry potential energy to the final energy production site.
The Inner Membrane: ATP Production
The final and most productive stage is oxidative phosphorylation, which is anchored to the folds of the inner mitochondrial membrane, called the cristae. This membrane is packed with protein complexes that make up the Electron Transport Chain (ETC). The NADH and FADH2 molecules deposit their electrons into these complexes, converting them back into their reusable forms (NAD+ and FAD).
As electrons move down the ETC, the released energy is used to pump hydrogen ions (protons) from the matrix into the narrow intermembrane space. This pumping action establishes a powerful electrochemical gradient across the inner membrane. Protons flow back into the matrix only through a specialized enzyme complex called ATP synthase. This movement drives the synthesis of a large quantity of ATP from adenosine diphosphate (ADP) and inorganic phosphate, a process known as chemiosmosis. Oxygen acts as the final electron acceptor, combining with the electrons and protons to form water, completing the energy-harvesting process.