Hi,

The potential decrease within ROS hyperproduction may be one of the results of the membrane auto-damage by autooxidation. If it is true, this effect must be soon interchanged with sharp fall of both potential and ROS production

Hi,

I was also wondering about a connection between the mitochondrial membrane potential (MMP) and superoxide production and came to the preliminary conclusion that there is no direct one. Here my thoughts on this matter:

In general, a higher membrane potential involves an increased activity of the electron transport chain and thus increases the likeliness of electron leakage causing superoxide production. However, you can get an increased MMP by blocking the ATP synthase with oligomycin A without a concomitant increase in superoxide production. In my opinion this is likely because the ETC comes to a halt once the MMP is sufficiently high. On the other hand, rotenone (complex I blocker) and antimycin A (complex III blocker) both reduce the MMP but cause superoxide production by preventing electron flow to ubiquinone thereby increasing the likeliness of superoxide formation (I have done these experiments in renal cell lines).

So in consequence, I think there is no direct connection between the MMP and superoxide that would allow you to draw conclusions from one parameter to the other.

I am happy to read what the community thinks!

Cheers,

Phil

Antimycin A stimulates superoxide production by the mitochondrial bc1 complex as it favours the production of reactive ubisemiquinone at the Qo site of this complex (oxidation of Qo-SQ is blocked by electron accumulation on the low potential chain of bc1 in the presence of AA). sO2 production by rotenone-inhibited Complex I is presumably due to flavosemiquinone- or ubisemiquinone production. 

A high membrane potential is also likely to impede transmembrane electron transfer from haems bL to bH in bc1 (delta E around 150 mV) as the electron has to work against the electrical gradient, once again promoting ubisemiquinone occupancy at Qo.