Credo

There was a line by karl in a  comment to my last post which triggered a summary of my current thinking about life and signals. A lot of this covers ideas I've had for a long time but not blogged about and, as I can never be sure a post will write itself, here is a thought dump to lay it out without any detail or references. As karl said:

"My hunch is the ROS signal is more primitive than insulin itself?"

In response:

Hi karl,

Superoxide is crucial to bacterial (and archaeal) growth, division and death.

Mitochondria retain this signalling system based on a bacterial ~200mV membrane potential.

The cell surface membrane (archaeal derived) has relinquished its 200mV potential to mitochondria.

Cell surface signalling still uses superoxide but this is now NOX controlled.

It provides the same signal as mitochondrial superoxide but has differing cues and locations.

Larger multicellular organisms use a pancreas to condense/combine these ROS signals in to a redox signal carried by a pair of -S-S- double bonds (ox stress marker, think of as a glutathione G-S-S-G mimetic) between two short peptides to encode and transmit an assessment of whole body redox status from the circulation, via the circulation.

Individual cells respond/resist this signal by making superoxide in response to it then modulate it using their own locally derived NOX/RET superoxide signals.

There is no need for it to be the insulin/insulin receptor combination that carries this signal, any -S-S- di-peptide and an appropriate receptor will do. Most metazoans use insulin/insulin receptor but plants, protozoa and yeasts made different choices but they all do the same job.

These assorted signalling systems cross react across all eukaryotes because the underlying ROS signal is fundamental.

Mitochondrial (bacterial style) ROS from RET in ETC -> mitochondrial division (biogenesis) = Good™.

Cell surface (eukaryote invented) NOX ROS -> cellular division -> tissue growth (+ cancer) = potentially Bad™.

Aside: Bad™ stolen from @KetoCarnivore on X/Twitter. End aside.

That LUCA, even before her division in to bacteria/archaea and while living in an anoxic hydrothermal vent, had a globin ancestor to bind O2, an SOD ancestor (based on Fe) to convert superoxide to H2O2 and a catalase to detoxify H2O2 suggests to me that O2 was available, rare/precious and used as a signal (by accepting an electron -> superoxide) of "membrane" potential (ie opportunity to grow, ie superoxide signal) which had to be processed and terminated at a time even before cell membranes were genetically specified.

Obviously catalase derived O2 would be re-stored by the globin for re-use. LUCA (in a deep anoxic ocean) would have derived a meagre supply of precious O2 from the radiolysis of water, a process still used by deep earth-crust bacteria living at a mile below the nearest O2 supply at the earth's surface, even today.

This is my most simplistic view. Without it I can't understand mice becoming obese eating an "high fat" diet. With it I’m spared the deeper intricacies of intermediary metabolism, a complex system if ever there was one.

Peter