How does shortage of oxygen halt the NADH dehydrogenase complex? I understand that in the absence of oxygen the functioning of cytochrome c oxidase stops because it is its substrate. However I don’t understand how stopping cytochrome c oxidase also stops the previous complex (the NADH dehydrogenase complex).

At a basic level this is quite straightforward if you look at an old-fashioned simplified diagram of the electron transport chain, such as the one below that I filched from the web.

![electron transport chain](

If oxygen is absent then there will be a build up of the reduced forms of each cytochrome. Starting from the bottom, in the absence of oxygen cytochrome _a_ is not reoxidized; if there is no oxidized cytochrome _a_ then reduced cytochrome _c_ cannot be reoxidized, and if there is no oxidized cytochrome _c_ then cytochrome _b_ cannot be reoxidized. The latter is the substrate of the NADH dehydrogenase complex — NADH-Coenzyme Q reductase in the figure — so this reaction stops for want of oxidised cytochrome _b_.

(Years ago I demonstrated on a standard undergraduate laboratory class using rat liver (or perhaps beef liver) mitochondria, where you inhibited different stages and detected the reduced forms by their colours in the visible spectrum.)