Mitochondria, Covid19 and Goldilocks

 

This post is a further exploration as to why bats can live with Covid and we cannot ... or can we?

In the UK at least 13-15% of the population have been found to be asymptomatic carriers of Covid19 and only shed virus ( ie are infective)  from time to time. In other words much like the bats from which the virus came, only as yet a smaller proportion of the population. 

Worldometer’s statistics show in the UK approx 40,000 deaths from 400, 000 symptomatics out of a population of 66,000,000. Whereas Uganda reports approx 80 deaths from 4,000 symptomatics and a population of 40,000,000.  This is an astonishingly smaller proportion of deaths.

Nothing, no mental gymnastics, no adjustments for reporting,  age and testing regimes will convince me that this difference is not showing a fundamentally different immune response to the virus in these populations. I also suspect that the virus is present in the population in vast amounts but that asymptomatic is the norm not the exception.

I suspect that the bats and the asymptomatic humans have one thing in common and that is a response to infection by this virus that falls into the ‘Goldilocks Zone’. That is just enough to keep the virus in check but not so much as to trip a cytokine storm. And, as is well known now, it is the cytokine storm that kills and that old age, obesity and high blood sugar that predisposes individuals to that fate.

Anyone who reads my posts knows that the role of mitochondria inevitably takes centre stage and this one is no exception. Forty year ago we were establishing the roleof mitochondria in bioenergetics which having been established eclipsed the signalling and control roles of mitochondria in the endo-ecology of the cell. I always wondered how the immune system knew a virus was inside a cell and doing its dastardly reproduction until finally bursting out of the lysed cell. Having done so this virus is in the bodily fluids, the animal is infectious and the immune system has some work to do … on the back foot so to speak.

I had not known about the signalling power of mitochondrial DNA (mtDNA). To cut a long story short some mitochondria develop a ‘hernia’. Herniated mitochondria as they are actually called have holes in their outer membranes which allow blebs of inner membrane to protrude and form vesicles which contain mtDNA probably in fragments. These migrate through the cytosol and are released into the surrounding fluids. Here they set off a chain of pro-inflammatory events leading to the formation of the ‘inflammasome’ which alerts the immune system. So far so good one can imagine a well ordered setup where the immune system deals with infected cells before metaphorically it all kicks off and starts the response which usually creates symptoms of illness.

It has been known for a very long time that mitochondria in senescent cells are more fragile and more leaky that those in younger cells ( I was 'blowing up' mitos with hypotonic shock in 1977!)  It is also well known that in middle age onwards in sedentary humans that a great many rarely used or unused muscle cells are ‘parked’ awaiting cell destruction (apoptosis) mediated by the mitochondria. The apoptosis is triggered by release of the contents of the mitochondria ( weakly bound Cytochrome C) via a complex set of signals.

It seems to me that viral infection into senescent and ‘limbo’ cells would quickly cause the mitochondria to leak drastically ending in apoptosis and mtDNA release. The most likely outcome of which would be a cataclysmic emergency response of the immune system.

So why are we in the UK so badly hit by this virus? Simply put we are older, fatter and more idle than our african dwellers. Older, equates to senescent leaky mitochondria, idle life styles equate to muscle cells in limbo ( sarcopenia is a common outcome of Covid19 patients)

Finally, obesity and diabetes equate to higher blood sugar which separately to the above is part of its own pro-inflammatory pathway. 

It looks like a ‘perfect cytokine storm’ is the price of  the modern life.

ps Intriguingly, a scenario as described above would paint an interesting picture for the very old but well individuals. They have experienced already substantial sarcopenia and so most senescent cells have gone. Also they have little body fat. I would love to know how many of them fail to succumb to the virus but the data has not yet fine-grained what is meant by old.