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Mitochondria in Type 2 Diabetes Patients Are Clogged with Defective Proteins, Scientists Find
Last reviewed: 27.07.2025
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Diseases of aging are associated with defects in protein synthesis and folding, including cancer, cardiovascular disease and type 2 diabetes.
Previous studies have shown that in patients with type 2 diabetes, proteins misfold in the insulin-producing β cells found in the islets of the pancreas. The resulting stress was thought to be primarily localized to the endoplasmic reticulum, an organelle responsible for the production and distribution of proteins within the cell. Ultimately, this stress leads to cell death.
In a new study published in Nature Metabolism, scientists at the University of Michigan found that mitochondria also accumulate misfolded proteins, leading to β-cell death. Reversing this process could help treat type 2 diabetes.
It was previously known that two proteins, insulin and amylin, often misfold in patients with type 2 diabetes. Both are produced by β cells:
- Insulin lowers blood glucose levels by helping cells absorb sugar.
- Amylin promotes a feeling of fullness after eating.
Amylin can form amyloid aggregates in the β-cells of diabetics, similar to the amyloid plaques seen in the brain in Alzheimer's disease.
“These two proteins have long been the only thing that’s been studied in islet cells from people with diabetes,” said Dr. Scott Suleimanpour, a professor of diabetes research and director of the Michigan Diabetes Research Center.
“We wanted to approach this question without bias and identify all the misfolded proteins in these cells.”
By sequencing genes and proteins in healthy and diabetic β-cells, the scientists found that the defense systems responsible for removing misfolded mitochondrial proteins are not activated in type 2 diabetes.
In particular, levels of the protein LONP1, which is responsible for removing damaged or misfolded proteins, were found to be reduced in cells from donors with diabetes.
"While LONP1 has previously been linked to rare mitochondrial diseases, this is the first study to show its role in type 2 diabetes," Suleimanpour said.
To confirm their findings, the researchers compared mice with and without an active LONP1 system. Mice without LONP1 had higher glucose levels and fewer β cells. These defects were reversed by reintroducing LONP1, suggesting that targeting this system could be a new therapeutic option.
“It’s clear that people with type 2 diabetes have problems removing misfolded proteins,” Suleimanpour added.
“The next step is to find drugs that can help fold or remove these proteins correctly.”
The group is also interested in studying the time course of type 2 diabetes. Because the disease often develops in adults, the scientists speculate that misfolded proteins may accumulate over time and eventually overwhelm the β cells, leading to disease. Early intervention may therefore be key.