Protein responsible for rare childhood disorder gives clues to common neurodegenerative conditions

A new mutation in the protein STAT2 has been identified in patients with mitochondrial disease. These findings could also be beneficial for more common neurodegenerative diseases, including Alzheimer’s, Huntington’s and Parkinson’s diseases.Mitochondria are dynamic organelles that constantly go through elongation (fission), and shortening (fusion) in order to share their genetic material and contents. There is a delicate balance between these fission and fusion events, which are very important for normal cell function. Modulation of this dynamic can lead to mitochondrial disorders.

The team identified a novel mutation in a gene called STAT2, which codes for a protein involved in the innate immune system, in two children presenting with severe neurological deterioration following viral infection. The researchers also observed that the mitochondria of these two patients and a third unrelated STAT2-deficient patient, appeared abnormally elongated in shape. Through studying the function of these organelles in the lab, the researchers were able to show that one of the proteins involved in mitochondrial fission is inactive in cells that lack the STAT2 protein.

These findings imply that STAT2 is a novel regulator of mitochondrial fission. It is also the first study to link the innate immune system to mitochondrial function. It is hoped that new therapeutic targets for mitochondrial diseases can be developed from these findings, for which currently there are no effective cure.

This study was led by BRC-supported Professor Shamima Rahman and is published in Brain.

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