SHIMURA Daisuke, Assistant Professor
When we hear that “the heart is failing” or “an organ is weakened,” we naturally imagine a problem at the organ level. That view is not wrong—but an organ is ultimately a complex “society” made up of countless cells. In many cases, the essence of disease is hidden in what happens inside those cells.
I have pursued my research from this perspective: understanding disease through the biology of the cell. In particular, I focus on mitochondria, the cellular organelles responsible for producing energy.
Power plants are essential—but also vulnerable
Cells need energy to function. Inside each cell, mitochondria act as “power plants” that generate the energy required for cellular work. However, this power generation comes with a cost. As mitochondria produce energy using oxygen, they can generate byproducts—like “sparks”—in the form of oxidative stress (for example, reactive oxygen species, ROS). Under normal conditions, cellular antioxidant and repair systems remove these byproducts. But during disease states or under excessive stress, this balance can collapse, and mitochondrial damage can contribute to loss of cellular function and even cell death.
An important point is that mitochondria are not simply static structures. They respond to their environment—such as energy demand and stress stimuli—by repeatedly undergoing fusion and fission, dynamically changing their shape and position to manage damage. Although fission is often associated with “breakdown”, in certain contexts, it may function as protective fission, isolating damaged portions and supporting recovery.
My research aims to discover new mechanisms that protect mitochondria under stress, and to define when, where, and how these mechanisms operate at the molecular level. In the project, I focus on a protein called GJA1-20k as a candidate factor that may support mitochondrial function by regulating mitochondrial morphology (shapes). I currently investigate how GJA1-20k helps maintain mitochondrial health under stress and how this may translate into cellular protection and stress resistance.
Controlling mitochondrial morphology to protect cells
Mitochondrial dysfunction is a common feature observed across many pathological conditions. If we can understand the cell’s intrinsic “ways of protection” and learn how to pharmacologically support these processes, we may be able to reframe disease not only as a “broken state,” but also as a condition that can be prevented, supported, and guided toward recovery.
In other words, if we can identify at which stage mitochondria begin to fail under stress, at which stage they can still recover, and which molecules contribute to protection, this knowledge may open new directions for future prevention and therapeutic strategies. As one entry point into this broader goal, I am particularly interested in the mechanisms that regulate mitochondrial fission.
Going forward, I hope to deepen our understanding of stress-response pathways—including those involving GJA1-20k—and to develop mitochondrial protection as a “common language” that is not limited to a single organ. Cells require energy to perform their work, and stable energy production is fundamental to life. I aim to advance both research and communication so that a wider audience can intuitively understand how mitochondria—the “small but central players”—shape health and disease.
