Mitochondria malfunction in ALS. But why these powerhouses fail in motor neurons remains unclear, making the design of energy-boosting therapies for the disease especially challenging (see July 2017 news).
Now, a research team led by Northwestern University’s Jane Wu in Chicago, Illinois reports that ALS-linked FUS interferes with the assembly of a key enzyme complex in mitochondria that produces energy – at least in inducible cellular and fruit fly models of the disease. What’s more, the unfolded protein response in these power plants is activated, potentially further contributing to mitochondrial damage and neurotoxicity.
The enzyme, known as ATP synthase (complex V), is also critical to fold up the inner mitochondrial membrane into “cristae”, key structures that help mitochondria produce energy efficiently.
The results comes at the heels of a previous study, led by King’s College London’s Caroline Vance in England, which found that defects in these power plants could be detected at pre-synaptic nerve terminals in a mouse model of FUS-ALS before the first signs of the disease (So et al., 2018).
The study appeared on September 24 in the Proceedings of the National Academy of Sciences.
The findings add to growing evidence that the buildup of FUS in the cytoplasm of motor neurons contributes to ALS by multiple mechanisms (see August 2013, October 2017, October 2017, March 2018, March 2018, September 2018 news).
To learn more about the emerging role of mitochondria in ALS, check out Targeting Mitochondria in ALS: Divide Less and Conquer?
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