Respiratory supercomplexes: plasticity and implications

Abstract

The plasticity model of the electron transport chain has slowly begun to replace both the liquid model of free complexes and the solid model of supercomplexes. The plasticity model predicts that respiratory complexes exist and function both as single complexes and as supercomplexes. The advantages of this system is an electron transport train which is able to adapt to changes in its environment. This review will investigate the current body of work on supercomplexes including their assembly, regulation, and plasticity, and particularly their role in the generation of reactive oxygen species and aging.

Figure 1

Possible pathways of SC assembly and the assembly factors involved are illustrated. The critical difference between the two major types of pathways is that one predicts that individual complexes assemble and then come together either individually or as the III/IV SC to form the I/III/IV SC while the other envisions the membrane arm of Complex I as a scaffold that subunits of Complexes III and IV can build on as Complex I assembly is completed.

Figure 2

Reactive oxygen species can cause three main types of damage in the mitochondria. ROS can peroxidize lipids which in the case of cardiolipin may be especially damaging to SC stability. ROS can also directly oxidize the complexes possibly affecting their ability to interact with each other, and finally ROS can cause mtDNA mutations which can affect the integrity of the MRC complexes. These three types of events over time may cause SCs to become unstable though evidence suggests that the higher order SCs may increase as a compensatory mechanism. Eventually however enough oxidative damage may make all SCs unstable. Complex I will then disassociate from SCs, and the amount of ROS produced by Complex I will increase causing a vicious cycle of oxidative damage.