NHLBI Orloff Award 2016: Brian Glancy

NHLBI Orloff Award 2016: Brian Glancy


Mitochondria is the main source of metabolism
in the muscles. What your mitochondria do is, they take the
fuels that you eat, and then they convert the energy from the fuel — whether it’s fat
or carbohydrates — they convert that energy into the type of energy that you need to fuel
your muscle contraction. Don’t have mitochondria, you don’t have movement. I’m Brian Glancy, investigator from the Muscle
Energetics Laboratory. Muscle energetics is how your muscle uses
energy in order to be able to move. My whole life I’ve been interested in both
sports, but I’ve also been interested in math and science. So when I was trying to think of, “Okay,
what type of career do I want to do?” — studying muscle metabolism, energy metabolism
became a natural fit for me. In muscle cells, there’s a lot of mitochondria
on the edge of the cell. Big amounts of mitochondria, they’re not near
the contractile parts of the muscle fiber. And so the question was, how does the energy
that those mitochondria produce, how does it get actually to the contractile proteins
that are going to contract and actually make your muscles move? So, what most scientists thought was that
energy moved throughout muscle cells, primarily according to diffusion or facilitated diffusion,
which is similar to if you drop some ink into a glass of water, and the way you see it slowly
spread throughout the glass of water. And so, we thought maybe that they were connected
in some type of way. We started to look at the muscle fiber in
three dimensions, with really high resolution images, and what we found was that these big
pools of mitochondria along the edge of the cell, they actually had little processes,
little wires coming out of them that went deep into the middle of the muscle fiber to
the parts of the muscle where the contractile proteins are actually connected to the mitochondria
on the inside of the cell, where you actually need to send the energy to fuel muscle contraction. Eventually, we found a method that we could
change the electrical voltage in the middle of the cell, and to see what would happen
in the areas outside that area. So, the theory would be that if they were
all electrically connected, if we change the voltage in the middle, then we should see
a change, the mitochondria on the outside of the cell. And what happened was, when we lowered the
voltage in the middle of the cell, the voltage lowered everywhere and all the mitochondria
surrounding it, and so that was our evidence that the mitochondrial network was all connected
electrically. There’s a lot of different things that this
opens up. One is to start looking at other types of
cells, like the heart, for example, to see if are there electrically coupled mitochondrial
networks there. The other thing that it does is it can provide
potentially new targets for people that have mitochondrial diseases, or they have some
kind of low-functioning mitochondria. So really, what it does is it gives us a whole
bunch of new things to go after to try to find targets to help people.

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