This could be one of the earliest steps, which subsequently causes many other pathways to be dysregulated, and could provide a new therapeutic target. Chronic kidney disease affects millions of people with diabetes, obesity and hypertension. If there's a way to address it early on, it might be a very good way of preventing damage to the kidneys."
Dr Afshan Malik, Reader in Mitochondrial and Diabetes Research
27 November 2024
Mitochondrial mechanism provides possible new target for Chronic Kidney Disease
Researchers have discovered a mechanism in our cell’s mitochondria that may shine a light on the early stages of Chronic Kidney Disease (CKD), offering potential new therapeutic targets.
The study, published in Molecular Medicine, reveals how two genes named NSA2 and GFM2 are controlled in similar ways, and that these genes are altered in patients with CKD.
CKD is a long-term condition where the kidneys do not work as well as they should. It can be caused by conditions such as high blood pressure, diabetes and high cholesterol and in some patients can progress to kidney failure. It also increases the risk of cardiovascular diseases, such as heart attack and stroke.
Our cells contain mitochondria that produce most of the chemical energy needed to power the rest of the cell. It was long believed that mitochondria operate independently from the rest of the cell, but more recent research has found that it is more closely associated with the rest of the cell that previously thought.
The genes NSA2 and GFM2 are linked to ribosome function, which are akin to factories in our cells that create proteins necessary for the wider cell’s biochemical reactions. Most of cells’ ribosomes are present in the cell’s cytoplasm but mitochondria also contain ribosomes that make proteins needed for energy production. Dr Malik’s group had previously shown that NSA2 was a potential biomarker for diabetic kidney disease, a common form of CKD.
PhD student Minjie Zhang discovered that the NSA2 gene is located next to the GFM2 gene, known to be a mitochondrial ribosomal gene, in humans and many other organisms. Research investigating mitochondrial dysfunction and CKD was already underway in Dr Malik’s lab, so a potential link between the disease, ribosomes and mitochondria was made.
The researchers looked at biopsies of human kidneys from patients with CKD and found that both these genes were altered. Both genes became more active in high glucose environments, like with diabetes, and were also switched on and off by zinc. Not only are these genes controlled in the same way, it was noted that their alterations could affect the cells’ health.
Another aspect of the research involved increasing the expression of GFM2. This resulted in a decrease in energy production, which then impacted the rest of the cell – a problem often seen in CKD.
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Reader in Mitochondrial and Diabetes Research