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Mice with disrupted mitochondria used to model Parkinson’s disease

Mice in which organelles called mitochondria are disrupted in vulnerable neuronal cells provide a new model of Parkinson’s disease. The pattern of neurodegeneration challenges long-held ideas about the disease’s motor symptoms.
  1. Zak Doric

    1. Zak Doric is at the Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, California 94158, USA, and at the Graduate Program in Neuroscience, University of California San Francisco, San Francisco.

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  2. Ken Nakamura

    1. Ken Nakamura is at the Gladstone Institute of Neurological Disease, Gladstone Institutes, San Francisco, California 94158, USA, at the Graduate Program in Neuroscience, University of California San Francisco, San Francisco, and at the Graduate Program in Biomedical Sciences and in the Department of Neurology, University of California San Francisco, San Francisco.

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Mitochondria — the cellular organelles crucial for energy production — have long been thought to be disrupted in the neurodegenerative disorder Parkinson’s disease. Mitochondrial function relies on the activity of various enzyme complexes, and dysfunction of complex I in particular has been implicated in Parkinson’s disease. Writing in Nature, González-Rodríguez et al.1 report that they genetically engineered mice to lack the gene encoding a complex I subunit called NDUFS2 in neurons that produce the neurotransmitter molecule dopamine. One of the brain regions that has dopamine neurons, the substantia nigra, contains the neurons that die first in individuals with Parkinson’s disease. The mice lacking NDUFS2 show neurodegeneration, providing a model of Parkinson’s disease (named the MCI-Park model) based on mitochondrial dysfunction. Moreover, the authors’ findings challenge the long-held idea that loss of dopamine release in the target structure of substantia nigra dopamine neurons, a brain region called the striatum, is sufficient to elicit the movement deficits associated with Parkinson’s disease.

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Nature 599, 558-560 (2021)

doi: https://doi.org/10.1038/d41586-021-02955-z

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Competing Interests

The authors declare no competing interests.

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