Thursday, August 27, 2020

Protons (59) The NDI1 guys and gals are good

This little chap:

featured in this paper

Mitochondrial ROS Produced via Reverse Electron Transport Extend Animal Lifespan

which I discussed here. Obviously a group which can get the above image in to a Cell Metabolism paper has an admirably relaxed outlook on their own work and probably on science in general. You have to be good to have that mindset.

So now they have given us this review:

Role of Mitochondrial Reverse Electron Transport in ROS Signaling: Potential Roles in Health and Disease

which really summarises, at the most basic level, the nuts and bolts of what is happening to drive RET in the ETC under assorted inputs. The Protons starting point.

Edit: I've just fixed a broken link in Protons (03) Superoxide. Back in 2008 I was just starting to tease out the differences between glucose oxidation and lipid oxidation and the initial paper which started me on superoxide was this one from Muller et al

High rates of superoxide production in skeletal-muscle mitochondria respiring on both complex I- and complex II-linked substrates

Once you twig that palmitate always drives complexes I and II but linoleate doesn't drive complex II so much... The NDI1 people make this soooooo much easier that it was back then. End edit.

They even found DHODH as another input (dihydroorotate dehydrogenase, I had to look it up too). Section A shows high ATP demand, low delta psi, minimal RET. Section C shows what happens when supply of nutrients exceeds ATP demand, delta psi rises and RET increases.

They've also got the TCA and beta oxidation working in parallel, as they do:

and have included the NADH:FADH2 ratios (admittedly upside down but I'm not complaining).

I hope their next move is in to subtleties of chain length and saturation to start to see how fatty acids have different ROS generating potential.

Then to relate ROS to insulin secretion/signalling. Insulin to obesity. Physiological vs pathological insulin resistance. Maybe metformin too.

But it's a great start. These people will go far.



BillyHW said...

Speaking of Cell Metabolism, have you read this paper yet from August 7, 2018:

Evidence for a Non-leptin System that Defends against Weight Gain in Overfeeding (author Yann Ravussin...)

The same author seems to have a couple other interesting papers, but I haven't seen anyone in the low carb community talking about them. They seem important to me.

Peter said...

Nice, thanks. Ultimately there is no such thing as ad-libitum over feeding. Ad-lib overfeeding is a synonym for hunger. They are looking at things from a potentially useful perspective....