A team of researchers at Johannes Gutenberg University Mainz (JGU) has discovered a mechanism that leads to mitochondrial dysfunction in Alzheimer’s patients, ultimately reducing the amount of energy supplied to the brain. According to Professor Kristina Friedland of the Institute of Pharmaceutical and Biomedical Sciences at JGU, this outcome is due to an RNA modification that has not been previously documented.of producing energy. They are crucial for maintaining the normal functioning of the brain. The researchers discovered that in Alzheimer’s disease, the mitochondria in brain cells experience a functional disorder. This leads to a decrease in energy production and an increase in oxidative stress. The dysfunctional mitochondria are also unable to properly regulate calcium levels, which is essential for normal cell function. This study provides valuable insights into the underlying mechanisms of Alzheimer’s disease and could potentially lead to new treatment strategies in the future.The body and especially the brain rely on the provision of energy, with 95 percent of the brain’s energy coming from the metabolism of glucose in the mitochondria. It is well-established that Alzheimer’s disease is associated with impaired glucose metabolism in the brain, which is caused by dysfunctional mitochondria due to aging and the accumulation of amyloid-beta.
The formation of adenosine triphosphate (ATP) as an energy source occurs in the inner mitochondrial membrane through a series of reactions known as the respiratory chain, involving over one thousand different proteins.There are proteins that are moved from the cell nuclei to the mitochondria, as well as proteins that are produced by the mitochondria themselves. One example is ND5, which is a part of complex I of the respiratory chain, according to Professor Kristina Friedland. NADH supplies electrons to complex I, which then transfers them to ubiquinone, creating ubiquinol. During this process, four proteins are moved from the matrix to the intermembrane space. ND5 plays a crucial role in this process, and mutations in the mitochondrial gene for this subunit can lead to serious mitochondrial disorders, such as L.
The research has shown that methylation can occur in the mRNA responsible for producing a protein involved in Leigh syndrome. mRNA is essential for carrying genetic information and translating it into proteins within the body cells. Methylation changes the chemical structure of mRNA, disrupting its interaction with tRNA and ultimately impacting the synthesis process. This leads to a reduced formation of important proteins such as ND5 subunit, which plays a crucial role in complex I of the respiratory chain, as explained by Friedland.
TRMT10C enzyme causes methylation which leads to the inhibition of ND5 synthesis. The Institute of Pharmaceutical and Biomedical Sciences at Mainz University conducted a study that revealed the enzyme TRMT10C is responsible for this methylation and subsequent suppression of ND5. The researchers observed a decrease in the production of ND5 proteins in a cell model and in the brains of Alzheimer’s patients. The findings were published in the journal Molecular Psychiatry, where the authors highlighted TRMT10C’s role in inducing m1A methylation.methylation of ND5 mRNA results in dysfunction of the mitochondria. The study indicates that this newly discovered mechanism may play a role in Aβ-induced mitochondrial dysfunction. This research was supported by funding from the Collaborative Research Center / Transregio 319 “RMaP: RNA Modification and Processing.”
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