mitochondrial matrix

Meaning: The matrix is the gel-like space inside the inner mitochondrial membrane. It contains the pyruvate dehydrogenase complex, the citric acid cycle enzymes (succinate dehydrogenase is the exception, embedded in the inner membrane as Complex II), fatty acid β-oxidation enzymes, mitochondrial DNA and ribosomes. These pathways produce NADH and FADH₂, which feed the electron transport chain. The chain pumps H⁺ from the matrix into the intermembrane space, so the matrix has a lower [H⁺] (higher pH) and is electrically negative relative to the intermembrane space. H⁺ then flows back down its gradient through ATP synthase, whose catalytic F1 portion faces the matrix, so ATP is made on the matrix side.

On the MCAT: Passages ask where a reaction occurs (pyruvate → acetyl-CoA, the citric acid cycle and β-oxidation in the matrix; glycolysis in the cytosol). They also ask you to predict what an inhibitor or an uncoupler does to matrix pH, the gradient or ATP synthesis. Because the inner membrane is impermeable to NADH and H⁺, cytosolic NADH needs shuttles to pass its electrons inward.

Common confusion: Students put the proton buildup in the matrix. Protons accumulate in the intermembrane space, and the matrix is depleted of them. Also, the outer membrane is fairly permeable, while the inner membrane is the tight barrier.