Derek Lowe's commentary on drug discovery and the pharma industry. An editorially independent blog from the publishers of Science Translational Medicine . All content is Derek’s own, and he does not in any way speak for his employer.

Here’s a weird one for you – one of those papers that, if it holds up, will make us all wonder about just how much we really know about cell biology. It’s from the IRCM at Montpellier, along with another INSERM lab (Gustav Roussey) and a lab at the Jacques Monod Institute at the Univ. of Paris, and the authors report that they can detect naked mitochondria floating around in blood samples. They appear to be still competent to do cellular respiration, and why they’re out there is anyone’s guess.

People had reported finding extracellular mitochondrial DNA, and it’s been studied as a potential diagnostic marker. That’s a mystery all by itself, because compared to nuclear DNA, mitrochondrial DNA is a much simpler circular species (reflecting its ancient origins from the days when mitochondria were free-living bacteria all their own that took up residence inside early eukaryotic cells). You’d think that it would be pretty rapidly degraded, and this new paper, in fact, started out as a hunt for what sort of structures might be containing it out in the blood. What I don’t think that they expected as an answer was “whole mitochondria, of course”.

You can see these things in plasma samples using dyes such as Mitotracker, and the intact nature of the mitochondria were also confirmed by electron microscopy. At least some of them are still doing their respiratory thing, but from the detection of smaller mitochondrial DNA pieces, it appears that they do get degraded by unknown mechanisms out there as well. This ties in well with the realization in recent years that mitochondria are in fact be transferred from cell to cell under normal conditions. It would appear that this transfer could be taking places over longer distances than anyone realized!

There are clearly implications for cellular communication, for inflammation, and for several other processes as well, but what I’m taking away from this paper is that for decades we have been missing the fact that normal whole blood apparently has ordinary mitochondria floating around in it. As usual when something like this turns out, my thoughts turn to what else we’re missing!

Addendum: since I mentioned the ancient event that brought mitrochondria into the cell, it’s worth nothing that a recent paper describes the first successful culture of an “Asgard” archaea organism (commentary here). It’s quite a feat of microbiology – when you read into the paper, you find that it took around twelve years to establish the culture in the lab. The organism is extraordinarily slow-growing and picky, but then again, it’s a very weird creature (as are the Archaea in general). There’s a good bit of evidence, which this paper is now able to add to greatly, that the very nuclei of eukaryotic cells came about through another such organism fusion. The paper’s figure 5 has a possible mechanism, whereby a bacterial species and an archaeaon fused together in the distant past, with the former eventually becoming the mitochondrion inside a larger eukaryotic cell and the latter becoming a primitive nucleus. When you’re looking at a human cell, you’re looking at the union of things that were once very, very far from humans indeed. . .