Why is succinate dehydrogenase attached to the inner mitochondrial membrane? Succinate dehydrogenase is attached to the inner mitochondrial membrane. All the other enzymes of the Krebs cycle are located within the matrix of mitochondria, though. In biological systems, there is often a relation between structural properties and function. For example, two enzymes that function sequentially in a metabolic pathway are sometimes held in close proximity to one another by a scaffold (e.g., in fatty acid synthesis). Is there a similar biochemical reason why succinate dehydrogenase is attached to the inner mitochondrial membrane, as opposed to being dissolved in the mitochondrial space?

The reason behind this lies in the properties of FAD+. Unlike NAD+, FAD+ is not free to diffuse within the mitochondrion, it is an integral part of the inner mitochondrial membrane. Its reduced form FADH2 contributes electrons directly to ETC.