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α-Synuclein and Mitochondria: Partners in Crime?

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Neurotherapeutics

Abstract

Increased α-synuclein levels and mutations in mitochondria-associated proteins both cause familial Parkinson’s disease (PD), and synuclein and mitochondria also play central, but poorly understood, roles in the pathogenesis of idiopathic PD. A fraction of synuclein interacts with mitochondria, and synuclein can produce mitochondrial fragmentation and impair mitochondrial complex I activity. However, the consequences of these mitochondrial changes for bioenergetic and other mitochondrial functions remain poorly defined, as does the role of synuclein–mitochondria interactions in the normal and pathologic effects of synuclein. Understanding the functional consequences of synuclein’s interactions with mitochondria is likely to provide important insights into disease pathophysiology, and may also reveal therapeutic strategies.

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Acknowledgments

This work was supported by a Burroughs-Wellcome Medical Scientist Fund Career Award, the Michael J. Fox Foundation for Parkinson’s Research, and award numbers 1KO8NS062954-01A1 and P30NS069496 from the National Institute of Neurological Disorders And Stroke. I thank Anna Lisa Lucido for assistance editing the manuscript.

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  1. Gladstone Institute of Neurological Disease, 1650 Owens Street, San Francisco, CA, 94158, USA

    Ken Nakamura

  2. Department of Neurology and Graduate Programs in Neuroscience and Biomedical Sciences, University of California, San Francisco, San Francisco, CA, 94158, USA

    Ken Nakamura

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Nakamura, K. α-Synuclein and Mitochondria: Partners in Crime?. Neurotherapeutics 10, 391–399 (2013). https://doi.org/10.1007/s13311-013-0182-9

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