More than a Powerhouse: Research Focuses on Mitochondria and their Response to Exercise

Mitochondria are most famous for their role as the “powerhouse of the cell.” These tiny membrane-bound organelles reside within nearly every cell within the human body, and they produce most of the chemical energy needed to drive cellular function. But mitochondria are more than an energy source. In many ways, they are vital to our body’s survival.

Depending on the amount of energy needed to operate, different cells contain different amounts of mitochondria. For example, high-energy organs like muscle, heart, liver, kidney, and brain contain a large number of mitochondria within their cells. If mitochondria function is disrupted, less energy is produced, and an organ can begin to suffer.

More than the Powerhouse

Joon Park, PhD, is an Associate Professor for the Department of Health, Human Performance, and Recreation (HHPR), within Baylor University's Robbins College of Health and Human Sciences. Most of his research focuses on mitochondria and how they respond to various levels and types of exercise.

“Recent scientific advancements reveal that mitochondria have functions even beyond ATP synthesis or oxygen consumption or energy production,” Park said. “Now we understand that mitochondria control the life and death of the cell. Mitochondria bring about the processes that can cause the biological energy to leave the cell. At a certain point, when cells have irreversible, severe damage, mitochondria turn on a process that can sacrifice those sick cells to keep other cells healthy.”

As cells age or become sick, mitochondria prompt them to die off on their own. This programmed cell death allows the body to control its homeostasis by maintaining healthy cells, but sometimes this process doesn’t happen. For example, cancer cells form when normal cell DNA is damaged, and they begin to grow uncontrollably. Healthy mitochondria can help decide which cells are destroyed by signaling molecules and turning on specific cellular processes that kill sick cells.

As an exercise physiologist, Park is connecting the processes of mitochondria with exercise. Research shows that routine exercise can make mitochondria healthier by improving regulatory function and providing our body a tolerance to different stresses. A lower tolerance can potentially increase your chance of developing a chronic disease.

“Sometimes we view exercise as mitochondrial medicine, because exercise improves function of mitochondria,” Park said. “Through those mechanisms, our bodies are getting stronger and healthier. That's kind of a common premise of our research.”

For the past 10 years, Park’s research projects have been funded by the National Institutes of Health (NIH) and the American Heart Association (AHA). The underlying molecular mechanisms of exercise, and its benefit to our cardiovascular system, are largely unknown. To help shed light on these mysteries, Park is striving to understand and redefine exercise at the cellular and tissue levels. In other words, Park is evaluating exercise at a stage beyond moving your body or playing a sport. He is looking under the skin to see how exercise impacts our physiology and, ultimately, benefits our mitochondria, which in turn improves our health.

In one study, Park is examining the effects of exercise on blood vessels. As heart rate and overall cardiac output increase during exercise, more blood flows within our circulatory systems. The increased blood flow brings friction on the blood vessel, which leads to increasing mitochondria size.

“For the blood vessel, exercise can be a mechanical stress caused by increasing blood flow in a certain area,” Park said. “In my lab we are trying to simulate this physiological condition in a dish. We grow the blood vessel cells and mimic the inner surface of the blood vessel. Then, we apply different magnitude and patterns of flow on top of the blood vessel tissue that we grew. We can isolate DNA and RNA proteins, and we can observe mitochondria in the growing cells under different types of physiological stress. In that way, we can see in the micro world how exercise works to improve the function of certain tissues or cells.”

The goal of this line of research is to identify the molecular transducers that collect all the stress from exercise and deliver that signal to the downstream cellular pathways, thus determining the exact process by which exercise improves the overall health of the cells and our body. So far, Park has identified several potential target molecules which seemingly contribute as the transducer of exercise at the cellular level: TFAM, TP53, PGC-1alpha, and PHD2. These findings have been published in high-impact biomedical journals such as Journal of Clinical Investigation Insight, Circulation Research, Redox Biology, and Journal of Physiology.

A long-term goal for Park’s mitochondria research is to translate his discoveries into practical means to help people improve their health. He hopes to eventually identity a protein that could improve mitochondrial function, just like exercise does. This discovery could lead scientists to synthesize those proteins for creation of an exercise mimetic or supplement.

“I don't believe that exercise drugs can replace physical activity because exercise has such multi-factorial effects in our body,” Park said. “But perhaps certain supplements or molecules, when combined with exercise, can amplify the effects of exercise for a certain population, like the elderly or someone who has disability or who really cannot participate in the regular practice of physical exercise.”

Mentorship and Collaboration

Park joined the Baylor faculty in July 2022. In addition to his research, Park is also passionate about STEM education and has enjoyed the “unique opportunity” to interact and partner with students in the lab.

“I am really interested in working with the younger generations to develop their talents and capacity and to help them achieve their own goals,” Park said. “At Baylor, I have the opportunity to do this.”

Prior to arriving at Baylor, Park taught at Temple University in Pennsylvania. There, he met and collaborated with graduate assistant, Ben Meister. When Park relocated his research lab to Baylor, Meister chose to follow and is now a PhD candidate in the Exercise and Nutrition Sciences program within the Department of Health, Human Performance, and Recreation.

At Baylor, Meister and Park are looking at the “crosstalk,” or communication, between skeletal muscle, endothelial cells, and blood vessels. Their study is related to peripheral arterial disease (PAD), a condition in which plaque builds up and causes the arteries to become narrow. This narrowing reduces blood flow and oxygenation to a person’s limbs and can cause pain in those limbs.

“What I'm looking at in this project is the mitochondria, specifically. I suspect that there may be something during an exercise that's beneficial in signaling from the blood vessels to the muscles that would actually help prevent that disease,” Meister said. “The goal at the end of the day is to hopefully eliminate some of the symptoms that may be happening in those disease populations, in addition to improving quality of life long-term for any patients or populations that may be struggling with these diseases.”

Mentoring the next generation is important to Park, and he helps guide the students he works with into becoming successful researchers. Through his work with graduate and undergraduates, he has discovered that mentoring is a two-way street – he often learns from his students, too.

“Research is a way of thinking. The younger generations have the right questions for research. But, because they are less experienced, they sometimes do not know how to address the question,” Park said. “Interacting with undergraduate students is not just teaching them lab techniques. It is teaching them a way of thinking, a way of doing research, so they can learn to answer their own questions.”

In addition to Meister, Park is also mentoring Liberty Tucker, a Baylor pre-med undergraduate student. Tucker is currently participating in the National Institute for Health’s Short-Term Research Experience Program to Unlock Potential, or STEP-UP. For the program, she decided to focus her research on diabetes and mitochondria in brain tissue under hyperglycemic, or high blood sugar, conditions. As a person with Type 1 diabetes herself, this project is personal for Tucker.

This past summer, Park and Tucker used mice models to compare the synaptosomes in the central nervous system between mice who are and who are not producing insulin, to see if the mitochondrial function differs. Microscopic imaging will also help provide insight into whether the mice’s brains developed structural differences, possible signs of oxidative stress, or inflammation, which also relate to mitochondrial dysfunction. Park and Tucker hope this study will help expand upon the potential impact on cognitive and memory function—or perhaps open new questions for them to follow.

“Dr. Park has just been awesome in helping to guide and teach me along the way. He is teaching me so many different techniques and is helping to show me exactly how to create an experimental design,” Tucker said. “It took so many months to create the protocol for the synaptosomes isolation, which taught me how to restructure my thinking process—to think like a researcher.”

Combining mentorship and research is important to Park, and he hopes collaboration will inspire a breakthrough for mitochondria and our health. He also recognizes working at a R1 research institution provides significant opportunities, and having access to cutting edge equipment for biomedical research and state-of-the-art facilities will play a key role.

“There is a lot of potential for research growth at Baylor,” Park said. “The research support from Baylor leadership is tremendous.”