Researchers at the University of Illinois developed a minuscule probe that can take the temperature of a cell’s interior. They used it to learn more about how heat is involved in metabolism. The power-generating organelles of the cell, mitochondria (described in the video below) have a sort of internal battery, which produces heat when protons are released. The researchers were able to take measurements of this heat. The findings, which may offer new insights into obesity and cancer, have been reported in Communications Biology.
"Producing heat is part of the mitochondria's role in the center of metabolism activity," said mechanical science and engineering professor Sanjiv Sinha, who led the work. "It needs to produce the energy currency that's used for the activities in the cell, and heat is one of the byproducts, in most cases. But there is a mechanism that can ramp this process up to produce more heat when the body needs it. That's what fat cells do when they're in need of heat when the body's temperature goes down."
The fast-read thermometer probe that was created had to be long enough to get into cells while they were viewed under a microscope. But it also had to be so small that it didn’t disrupt the cell’s functions.
"Think about how we take temperature with a probe under our tongue. We are essentially doing the same, but inside a single cell," Sinha said. "And we wanted to be very fast to measure what's happening. Things happen inside the cell very quickly. It's like, if you're taking a young child's temperature, you need to do it very quickly, or they will move and it won't be accurate."
Along with with the lab of emeritus professor Rhanor Gillette, Sinha’s team tested their probe, which turned out to be surprisingly effective.
"We found some results that were completely different from what has been published before," noted Manjunath Rajagopal, a graduate student and first author of the study. "We saw a sharp temperature spike that is significantly large and short-lived - around five degrees Celsius and less than one second. The gold standard for measuring has been with fluorescence, but it is too slow to see this short, high burst of heat. Just with a simple probe measuring at high speed, we have demonstrated that we can find things that other methods have missed."
It was thought that mitochondria were producing heat as they broke down more glucose. However, the heat spikes the researchers were observing were too high for that. "It cannot be releasing that kind of energy from metabolizing stored glucose. It just didn't make sense," Sinha said. "Where is it coming from? There has to be a source of that energy."
After hypothesizing that the energy release was akin to the release of protons from a cellular battery, the team confirmed it using molecules that open membrane channels in the mitochondria.
"In the mitochondria, one part of the glucose metabolism reaction stores some of the energy as a proton battery. It pushes all the protons to one side of a membrane, which creates an energy store," Rajagopal said. "We basically short-circuited the stored energy."
The team wants to apply the probe to more types of cells, which may reveal targets for therapies. Fat cells, for example, might be stimulated to release protons as an obesity treatment.
"Cancer would be another application," Rajagopal said. "Cancer cells have a variety of reprogrammed metabolic pathways that are often driven to extremes. This probe provides us a tool to study thermal activity associated with different metabolic pathways."
Learn more about the role of mitochondria in disease from the video.