The Quiet Branches

Give up on that riddle?

Well, you’re right in thinking there’s not a lot in common between them. All life is connected, however, some is just further apart on the evolutionary bush than others. One is an animal, one is a plant. A lot of evolution and an endosymbiont (the chloroplast plants have that animals don’t) separate them. However, there is a narrow way the two are alike. Let’s dive in.

Naked mole rats are odd creatures whose name really describes them well. They are also remarkable in many ways. Last Month in Science, a study was published about how they are able to live in underground colonies where oxygen is scarce (as low as 6%) and carbon dioxide (CO₂) can build up since like us, mole rats exhale CO₂. This was one problem faced by the Apollo 13 astronauts who improvised a CO₂ scrubber. Naked Mole Rats can survive in these low oxygen, high CO₂ conditions and even be active under them. The conditions are part of burrow defense against predators needing open air.

The researchers exposed the Naked Mole Rats and mice to low oxygen — and even no oxygen— conditions where both lost consciousness, but the naked mole rats recovered quickly with no apparent ill effects. Lab mice didn’t fare as well and depravation was quickly lethal to them.

In some of the reporting on this study, the authors are quoted as saying naked mole rats metabolize the sugar fructose like a plant. From Kendra Pierre-Louis’ Popular Science report:

“One thing we’ve been horsing around with is the idea that the naked mole rat has an insect-like social structure like ants and bees,” said Park, “and it has a thermoregulation system like a reptile, and they metabolize fructose like a plant.”

What is the secret of the Naked Mole Rat’s low oxygen adaptation? And how is their metabolism plant-like?

One adaptation is naked mole rat hemoglobin, the protein that carries oxygen in most vertebrates’ blood is “stickier” than it is in other animals. When free hemoglobin  circulates through the lungs (inside red blood cells), naked mole rat hemoglobin is more likely to pick up inhaled oxygen molecules than a human or mouse hemoglobin molecule.

Another distinction is flexibility in metabolism.

That is the major finding in the Science paper. The work of converting the sugar glucose into energy starts with one of the most ancient pathways all cells have: glycolysis, or splitting sugar. One quirk of this pathway is that some compounds produced by it (citrate and the cell’s energy molecule ATP) feed back and inhibit the activity of one of the enzymes responsible for loading sugar into the sugar-splitting part of glycolysis. Fructose, by contrast, can get around this block because there is an alternate way it can get processed to fuel glycolysis, bypassing the negative feedback.

Most organs rely on glucose that gets modified with a phosphate to make glucose-6-phosphate and actually converted to fructose-6-phosphate to fuel their cells’ metabolisms. That is the sugar supplied to most of our cells and regulated by insulin in our bodies. An exception is in the livers of most vertebrates which does have the enzymes to modify fructose into a form where cells can bypass the block to fuel glycolysis.

Upon oxygen starvation, naked mole rats show a spike in sucrose (table sugar, that is one glucose and one fructose molecule linked together) and fructose (aka “fruit sugar”) in their blood under low oxygen conditions and they switch on fructose transporters and enzymes to bring in and feed fructose into glycolysis in not just their liver cells, but all of their cells, including the essential brain and heart. Fructose is modified into fructose-1-phosphate and then fructose-1,6-bi-phosphate which is the molecule that gets split in glycolysis that generates ATP and other molecules needed for downstream metabolism.

In plants, sucrose is the main sugar that transported around the plant after glucose is made in photosynthesis. Glucose and fructose have the same number and type of atoms, both are C₆H₁₂O₆, but arranged slightly differently. One can be converted to the other by an enzyme.

Like animals, plants respire, taking sugars and splitting them apart for energy and to generate other molecules essential to life. This occurs in all living plant cells. Plant cells also have two locations glycolysis can occur: in plastids like chloroplasts (where photosynthesis also occurs) and in the cytosol, the part of the cell that isn’t any other internal structure/organelle.

Naked mole rat achieves something similar, an ability to use fructose to fuel glycolysis in most tissues/organs, bypassing the feedback mechanism stopping too much glucose feeding into the glycolytic pathway.

So far, I haven’t mentioned where oxygen comes in.

Oxygen is not needed for glycolysis. It is only needed in a subsequent step in respiration, oxidative phosphorylation. Molecular oxygen (O₂) is oxidized, to ultimately create a differential pH gradient on either side of a membrane in the cell’s power plant, the mitochondria. The mitochondria attempts to restore equilibrium across the membrane driving the production of ATP, a cell’s main energy source. Without oxygen, components of glycolysis aren’t as efficient, and the amount of energy produced by oxidative phosphorylation where the lions share of ATP is generated, cannot take place. Glycolysis is better than nothing, but even that can’t be sustained forever, especially if glucose is the only sugar available to feed into it (that feedback block will come up). The Fructose naked mole rats can transport and process can continuously produce some energy under low oxygen conditions, permitting cells to survive and then recover when oxygen is restored.

The context of oxygen deprivation for plants is also slightly different. While plants do have roots in the soil that may not be well aerated (and oxygen within the plant is likely in sufficient supply; roots produce hollow cells that are meant to aerate below ground roots), as long as sugar from photosynthesis in the shoots is circulated, they’ll be able to survive.

However, plants do experience a lack of oxygen under flooding conditions (those air pockets in roots get flooded too). It’s a major problem for rice growers that grow rice in paddies that can get completely inundated (some parts of Southeast Asia are projected to have more flooding due to climate change). Some plants “hold their breath” or attempt to grow out of the low oxygen environment sufficiently to maintain themselves. In the former strategy, so-called ‘sub1’ rice exists that can tolerate flooding for two weeks and then resume growth, thus increasing yield of a field. The sub1 strategy is in some ways akin to what the naked mole rats do under oxygen deprivation, shutting down to a crawl, but maintaining enough energy to keep vital cells alive until oxygen levels return to normal, or at least functional levels.