In the last entry of The ETC Disassembled we described mitochondrial complex I (CI) and its fundamental role as the first component of the electron transport chain. In this second entry we will focus on the next link in the ETC; mitochondrial complex II.
A diagrammatic representation of ETC complex II indicating its shape and function. Source: wikipedia.org
Like all components of the ETC, complex II (CII) is an enzyme; namely succinate dehydrogenase. As illustrated above, the primary substrate of CII is succinate (sometimes known as succinic acid). CII is unique among mitochondrial enzymes in that its action upon its substrate molecule is essential for two separate biochemical processes. It is also the only ETC component that that does not contribute protons to the electrochemical gradient that powers ATP synthase.
Structurally, CII consists of a total of four sub-units; two hydrophilic sub-units (SdhA & SdhB) and two hydrophobic sub-units (SdhC & SdhC) that act as membrane anchors [1]. Like CI, CII exists partially embedded in the inner mitochondrial membrane with a projection into the matrix. CII integrates a molecule of heme into its structure. This heme is thought to play a role in both electron transfer and the proper assembly of CII [1].
The two enzymatic actions of CII are to: 1) oxidise succinate to fumarate and 2) reduce coenzyme Q10 (CoQ) to CoQH2 as denoted by the following equation:
Succinate + CoQ → Fumarate + CoQH2
This single reaction generates two products, each of which is required for a different biochemical pathway. CII generates CoQH2 to the same ends as CI; to drive the action of complex III. In this regard the two enzymes are similar, however the mechanisms by which they achieve this synthesis do differ slightly. Specifically, in CII the oxidation of succinate is mediated by flavin adenine dinucleotide (FAD), whereas in CI flavin mononucleotide (FMN) is the intermediary molecule. In both instances the electrons generated by the redox reaction are transferred to CoQ via series of iron-sulphur centres acting as a molecular ‘wire’. Both CI and CII could be considered as entry points for CoQH2 into the electron transport chain from two different sources, as they both contribute an identical product to a pool utilised further down the ETC by mitochondrial complex III.
As indicated above, the production CoQH2 by CII is mediated by the oxidation of succinate to fumarate. This action also serves as one of the steps in the citric acid cycle (illustrated below); the mitochondrial process that lies of the heart of eukaryotic energy generation. The actions of CI, CII and the citric acid cycle are intrinsically linked in that CII is necessary for the citric acid cycle to take place, and the citric acid cycle is responsible for generating the NADH required for the action of CI.
An illustration of the citric acid cycle. Note the CII-mediated oxidation of succinate in the bottom left. Source: wikipedia.org
References & Further Reading:
1 – Yankovskaya, V., Horsefield, R., Törnroth, S., et al. (2003) Architecture of succinate dehydrogenase and reactive oxygen species generation. Science 31 (link to article)
Mitochondrial Me 
