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Let's say that it's impossible for a hypothetical organism's proteins to denature - unfolding and loosing their structure - due to high heat, and that, as such, temperatures equal to those required for those proteins to denature no longer present a health hazard to said organism.

Additionally, let's say that this organism is an animal - one with an intestinal tract - and that its intestinal permeability scales with the body's thermoregulatory mechanisms; that is, when the temperature increases, the body decreases its intestinal permeability, preventing endotoxemia, and, therefore, also preventing sepsis.

Note that these things are handwaves. I'm going to soften them up a bit by claiming that this hypothetical organism also produces many more heat shock proteins - proteins designed to mitigate stresses on cells, including high temperatures - than normal, as well as producing high levels of cyclic 2,3-diphosphoglycerate and having lots of topoisomerase V (see below), but it's still a handwave.

The question: what's the next problem? After septic shock and protein denaturing are overcome, what's the next overheating-related thing to cause physical harm to/kill this organism?

Assume that, aside from those alterations, this is a multicellular, mammalian vertebrate that runs on Earth biochemistry - think "human".

I was inspired by this answer to a previous question of mine; in it, theorist points out that the bacteria M. kandleri has high concentrations of cyclic 2,3-diphosphoglycerate; moreover, its Wikipedia page points out that it is the only species to have topoisomerase V, which apparently enables it to survive at temperatures of up to 110 degrees Celsius/230 degrees Farenheit/383.15 Kelvin.

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  • $\begingroup$ mammalian cells already produce increasing levels of heat shock proteins indefinitely at elevated temps, so you'll need a different handwave. $\endgroup$
    – DWKraus
    Dec 20, 2021 at 14:23
  • $\begingroup$ Are denaturation and septic shock lower boundaries for this ? I've been looking around for multicellular animals resisting temperatures beyond the temperature of cell membrane degradation (45, see answer DWKraus), can't find them.. there are some theoretical options maybe, hope this link works, books.google.nl/… $\endgroup$
    – Goodies
    Dec 20, 2021 at 15:33

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45:

At about 45 degrees Celsius, cell membranes start to dissolve. Life forms with cell walls can use the structural support of the walls to maintain integrity longer, but multicellular animals will observe increasing membrane permeability until the membranes pop. Magic proteins may extend this slightly (since the channel proteins won't fail) but this is a really unhealthy temp.

High pressure might help. Pompeii worms can tolerate temps up to 80 degrees Celsius. but only part of the organism is exposed to these temps, and they have a symbiotic relationship with a "fleecy" bacteria that provide a sort of insulation.

Ah, you say. Tardigrades can survive temperatures up to 100C! Well, only for brief periods, and not in a functional state, but more like hibernation. I don't think your hypothetical human is okay with pickling themselves to survive briefly and unconscious at high temps. And damage a water bear might be willing to tolerate might be lethal or at least crippling to a large organism.

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  • $\begingroup$ The 45 degrees is max body temperature overall (max fever). The thermal denaturation which was overcome according to the question, starts higher: 47 degrees for the very first symptoms, range 47-83 degrees ref pubmed.ncbi.nlm.nih.gov/1722814 $\endgroup$
    – Goodies
    Dec 20, 2021 at 15:00
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    $\begingroup$ @Goodies that is in E. coli, a bacteria with a cell wall to reinforce the membrane. $\endgroup$
    – DWKraus
    Dec 20, 2021 at 15:23
  • $\begingroup$ Yes, more resilient because of that wall.. it is difficult to find multicellular organisms that can resist high temperatures.. even for e-coli, max is only 49 degrees pubmed.ncbi.nlm.nih.gov/16187264 $\endgroup$
    – Goodies
    Dec 20, 2021 at 15:31
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Assuming no other limiting factor (e.g. the availability of reactants, no other competing reactions starting, etc), as a rule of thumb, reaction rates for many reactions double for every ten degrees Celsius increase in temperature..

The above with all the consequences, with the most evident:

  • depletion of energy reserves due to thermal stress
  • competing reaction crossing the threshold over which the metabolism can compensate to maintain homeostasis
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  • $\begingroup$ Basically, it radiates energy away as heat too quickly to feed itself to compensate? $\endgroup$
    – KEY_ABRADE
    Dec 20, 2021 at 11:39
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    $\begingroup$ Basically, it happens no matter the cause of temperature increase: fever or water at 110 degrees Celsius. $\endgroup$
    – Adrian Colomitchi
    Dec 20, 2021 at 11:51
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This is where the water phase change problem begins. Increase in pressure and the possibility of an explosion of cells and, in extreme cases, tissues. Also remember about the increase in gas pressure in the digestive tract. The pressure will slightly raise the boiling point of the water, but not so much as to easily survive temperatures of 120-150 ° C. Even such a level requires the strengthening of the cell walls and some external source of increased pressure.

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  • $\begingroup$ You're telling me that this thing could get up to 100 degrees celsius? $\endgroup$
    – KEY_ABRADE
    Dec 20, 2021 at 11:40
  • $\begingroup$ Your cited bacterium, M. kandleri gets hotter still. You said that that was one of the limits (heat shock, mitigated by 2,3-diphosphoglycerate) which had been overcome and you were looking for the next. This seems to be the next to me. @KEY_ABRADE $\endgroup$
    – Escaped dental patient.
    Dec 20, 2021 at 11:54
  • $\begingroup$ @ARogueAnt. Well, this is a multicellular invertebrate, so I was kind of wondering if scaling it up to something vastly more complex would create issues. $\endgroup$
    – KEY_ABRADE
    Dec 20, 2021 at 11:55
  • $\begingroup$ There was a bacteria discovered on the wall of a black smoker from the Gulf of California, at a depth of 2000m. The environment was 84-110 degrees, in the laboratory it was found to be able to reproduce (!) at 122 degrees en.wikipedia.org/wiki/Methanopyrus .. it has its own special class in phylum en.wikipedia.org/wiki/Euryarchaeota $\endgroup$
    – Goodies
    Dec 20, 2021 at 15:08
  • $\begingroup$ On 2000m You have around 200bar pressure and boiling point around 210 ° C $\endgroup$
    – Kamitergh
    Dec 21, 2021 at 6:59

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