Revolutionary ATP Imaging Technique Sheds Airy on Energy Production by Kidney Cells

The incidence of kidney disease is rising in Japan, now affecting one in eight adults, but developing effective treatments remains a challenge. The kidneys are among the most energy-hungry organs in the body. To function, they constantly produce and utilize gigantic amounts of adenosine triphosphate (ATP), a chemical the body uses to store and transport energy. However, ATP dynamics—changes over time in the production and utilize of ATP—in the kidneys are poorly understood because of a lack of imaging technologies.

Using a newly developed ATP imaging system, the researchers were able to visualize the amount of ATP in different kidney cells, including the deeper segments of the nephrons, which are functional units in the kidney. This provides a detailed picture of how energy is generated and used in different parts of the kidney. The fresh system allowed the researchers to study ATP dynamics in real time using kidney slices taken from GO-ATeam2 mice, a genetically modified mouse model the researchers recently developed that expresses an ATP biosensor.

A key finding of the study was that there were distinct pathways for ATP synthesis in different segments of the nephron. They found that proximal tubules were highly dependent on oxidative phosphorylation (OXPHOS) for ATP production, whereas podocytes relied on both OXPHOS and glucose conversion. ATP production in specific segments suggests that targeting these pathways could lead to more effective treatment of kidney disease.

The researchers also used their imaging system to study ATP dynamics in disease models, including ischemia-reperfusion injury and chemotherapy-induced injury. They found that ATP levels in the proximal tubule were particularly affected in these models, underscoring the importance of energy metabolism in renal injury.

Principal investigator Dr. Shigenori Yamamoto emphasized the importance of understanding the intricate interactions between kidney cells when developing therapeutic strategies to improve kidney function.Experimental techniques that enable analysis of multiple cell functions over time, including our novel system, will be a powerful tool“notes.

The research team plans to further refine the imaging technique and utilize it to study ATP dynamics in various models of kidney injury, including those associated with diabetes, aging, and drug-induced injury. By better understanding the impact of ATP production in these conditions, they hope to identify fresh therapeutic targets and improve treatments for kidney disease.