Rac1 Protein: The Key to Damaged Kidney Repair

The kidney's proximal tubule reabsorbs water, glucose, ions and other small molecules from the urine and thus maintains the body's supply of these essential constituents. The tubule can be easily damaged by ischemia, or poor circulation, but it normally can repair itself. Discovery of Rac1's role in repair Now, researchers at Vanderbilt University Medical Center have discovered that a protein called Rac1 acts like a molecular switch to promote tubule repair. Their report, published in the Proceedings of the National Academy of Sciences, adds another role that Rac1 plays in promoting recovery of the injured kidney and suggests that Rac1-dependent mechanisms that control cell structure may be a therapeutic target for enhancing recovery from severe or extensive kidney damage. "These findings were unexpected and demonstrate that the actin cytoskeleton repairs cell organelles like mitochondria in a regulated way," said the paper's corresponding author, Fabian Bock, MD, Ph.D., assistant professor of Medicine and of Cell and Developmental Biology. Previous research and new findings Previously, Bock, Roy Zent, MBBCh, Ph.D., and their colleagues showed that Rac1 is essential for maintaining the integrity and function of epithelial cells lining the collective ducts, downstream of the proximal tubule. Last year they reported that this actin cytoskeleton regulator also drives repair of collecting ducts that have been damaged by obstructed urinary flow. In the current study, the researchers found that by promoting the formation of actin cytoskeleton inside the epithelial cells lining the proximal tubules, Rac1 facilitates removal and replacement of mitochondria damaged by ischemia. This restores cell structure, mitochondrial respiration, and energy production, thereby enabling the tubules to resume their normal function. Importance of mitochondria and actin cytoskeleton Mitochondria are organelles in the cell that, through a process called "respiration," convert nutrients into ATP, the cell's major form of energy. Because of the high energy cost of reabsorption, the cells of the tubule epithelium are rich in mitochondria and rapidly become atrophic if they don't work. The actin cytoskeleton is a dynamic structure that not only supports the cell but enables the movement of elements within it. Without Rac1, damaged mitochondria are not removed; energy production declines; and the cells atrophy. "The proximal tubule is a really important cell type in kidney health, and this data shows it strongly depends on organized and functioning mitochondria with little metabolic flexibility," said Zent, the Thomas F. Frist Sr. Professor of Medicine and professor of Cell and Developmental Biology.