Protons: Love your superoxide (outside your brain)

Two off topic posts in a day! How come? I had the weirdest morning today. A three hour consulting session with only six appointments, all straight forward. Bloody hell, was I lucky for a Saturday! Can't blog at work so I had a quick browse to see what Nick Lane has been up to recently. He has a cracking article up (as a pdf) on heteroplasmy which rewards careful reading in its own right, but look at these two "throw away" quotes.

First on ROS, good old superoxide from reverse electron transport:

"ROS leak seems to optimize ATP synthesis by stimulating mitochondrial biogenesis (mtDNA copy number), an interpretation supported by the fact that antioxidants lower not only ROS leak but also mtDNA copy number and ATP synthesis. ROS leak, in effect, signals low capacity relative to demand, stimulating compensatory mitochondrial biogenesis".

How do we minimise mitochondrial biogenesis? By running metabolism on glucose of course, but don't forget the lack of superoxide generation when oxidising PUFA. But who needs mitochondria when you can lower LDL levels by swilling corn oil? Ah cardiology, you have a lot to answer for. Executive summary: Want mitochondria? Burn PALIMTATE.

And on cerebral metabolism:

"In the brain, where further mtDNA biogenesis is limited, neurons would then become compromised whenever energy demands were high, possibly causing acute cognitive and behavioral abnormalities".

The brain neurons are running on lactate under crapinabag conditions. We considered this before. No fatty acids. No glycerol 3 phosphate. No FADH2 input to the CoQ couple. No free radicals. No signal for mitochondrial biogenesis. No mitochondrial biogenesis. You could substitute ketones and maybe get a few mitochondria back if you were canny, but most medics aren't canny. What happens to the lactate supply for neurons when hyperglycaemia drops on to chronically elevated FFAs and triggers apoptosis in glial cells? I think we can attach various labels, depending on which neuronal cell types die first. Alzheimers seems a nice name for the commonest scenario.

Lovely pair of quotes. Glad I got the browse time. But don't ignore the heteroplasmy discussion at the core of the article, it's good stuff.

Peter