Of Mice and (Wo)Men

Mitochondria are the powerhouse of the cell! Ok…but what do they do? Mitochondria are organelles present within almost every eukaryotic cell type. They are responsible for converting the nutrients that we consume—sugars, proteins, fats, etc.—into a form that can be used by every cell in our bodies to do cellular work. ATP is that universal energy currency of multicellular eukaryotic organisms produced by the mitochondria.

In the Brandauer lab, we are interested in studying metabolism and the effects of different types of interventions, like exercise, on mitochondrial biology.

There are a number of human diseases and disorders associated with metabolic dysfunction, such as diabetes, obesity, neurodegenerative diseases, cancer, and the aging process. Exercise is a known intervention that improves outcomes of individuals with many of these conditions, but the exact cellular details of how it’s done are still unknown. Current research is looking into the specific metabolic effects of exercise to discover the molecular processes responsible for the observed health benefits. From there, drug interventions that duplicate these effects can be created to treat metabolic diseases.

This summer, we are studying the effects of chronic exercise on metabolic function. To do this, we are quantifying nicotinamide adenine dinucleotide (NAD+) concentrations within different tissues using high performance liquid chromatography (HPLC). We will also be comparing the relative concentrations of mitochondrial proteins using Western Blotting.

NAD+ is a small molecule that functions as an electron carrier in metabolic reactions. It is essential in the set of reactions that harvest energy from fuel molecules, like glucose, and result in the production of ATP. NAD+ is also involved in mitochondrial biogenesis, meaning it is necessary in order to create new mitochondria within a cell. NAD+ concentration has been shown to be an effective measure of mitochondrial function. We hypothesize that, because a chronically exercised organism has increased energy needs, the rate of metabolic reactions and mitochondrial production will increase, leading to an increase in NAD+ within the cell.

Proteins of interest include sirtuins, a family of proteins involved in metabolic reactions that regulate gene expression and may help neutralize reactive oxygen species (ROS). ROS are a class of molecules produced through normal metabolism that, left unchecked, are damaging to cells and can contribute to the aging process and the development of cancer and other disorders. In order to perform these functions, sirtuins use NAD+ as a substrate in enzymatic reactions that degrade it into nicotinamide (NAM). This leads to another enzyme of interest called nicotinamide phosphoribosyltransferase (NAMPT), a protein involved in recycling NAM back into NAD+. We hypothesize that chronic exercise will lead to an increase in the proteins within the cell.

In order to test our hypotheses, we must first establish exercised and sedentary experimental groups of mice. While the sedentary mice get to nap all morning, the exercised group is put to work!

Thursday, June 8th marks the start of the third week of training, so we have ramped up the difficulty of their training to keep them working!

mice running

Our first group of 6 mice (out of 12 total exercised mice) getting their morning workout at 17m/min at a 5% incline.

mice napping

Our sedentary mice settling down for their morning nap!

After six weeks of training the mice, we will collect our samples and freeze them so that, when we come back in the fall, we can analyze them. We are honored to be included in this research and thankful to Dr. Brandauer, the XSIG program, and Gettysburg College for this opportunity!

Anna Salmonsen & Ashley Carvajal