How does cytochrome c oxidase inhibition cause cell death?

Question

I realise the inhibition of cytochrome c oxidase prevents the release of H+ ions into the intermembrane space, and that the ion gradient is required for ATP synthase action. However, I'm not sure how this causes cell death.

Does this:

a) Prevent oxidation of Cytochrome C, preventing electron movement the cytochrome bc1 complex, which in turn prevents electron movement from earlier parts in the chain, shutting down the electron transport chain altogether? Thus, no ATP is produced and the cell dies due to lack of ATP.

b) Prevent oxidation of Cytochrome C, but not preventing oxidation in the other protein complexes*, merely reduce the number of H+ ions available for ATP synthase action, lowering the amount of ATP produced, and the cell dies due to low ATP levels.

c) other.

I realise in either case, the ATP count is merely lowered, as ATP is produced by other methods, so my statement 'lack of ATP' is not totally explicit.

*This being the case, how are the released electrons dealt with by the cell? Are there electron acceptors to remove this?

Answer 1

Inhibition is rarely binary - it's almost always subjected to stoichiometric effects. So the answer could be either option, depending on the amount of the inhibitor present in the system. If there is a huge amount of the inhibitor in the cell, it may more or less completely ablate ATP production by the ETC.

On the other hand, if there isn't enough of the inhibitor to shut down all cytochrome C oxidase, you'd only see a reduction in the amount of ATP produced by the ETC (which could still be sufficient to kill the cell).

It also depends on the type of inhibition taking place. Is it reversible or does it bind permanently? Does it degrade quickly? These aspects are also important to consider.