Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain

Steven M. Graves; Zhong Xie; Kristen A. Stout; Enrico Zampese; Lena F. Burbulla; Jean C. Shih; Jyothisri Kondapalli; Tomasso Patriarchi; Lin Tian; Lars Brichta; Paul Greengard; Dimitri Krainc; Paul T. Schumacker; D. James Surmeier

doi:10.1038/s41593-019-0556-3

Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain

Steven M. Graves, Zhong Xie, Kristen A. Stout, Enrico Zampese, Lena F. Burbulla, Jean C. Shih, Jyothisri Kondapalli, Tomasso Patriarchi, Lin Tian, Lars Brichta, Paul Greengard, Dimitri Krainc, Paul T. Schumacker, D. James Surmeier

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Abstract

Monoamine oxidase (MAO) metabolizes cytosolic dopamine (DA), thereby limiting auto-oxidation, but is also thought to generate cytosolic hydrogen peroxide (H₂O₂). We show that MAO metabolism of DA does not increase cytosolic H₂O₂ but leads to mitochondrial electron transport chain (ETC) activity. This is dependent upon MAO anchoring to the outer mitochondrial membrane and shuttling electrons through the intermembrane space to support the bioenergetic demands of phasic DA release.

Original language	English (US)
Pages (from-to)	15-20
Number of pages	6
Journal	Nature neuroscience
Volume	23
Issue number	1
DOIs	https://doi.org/10.1038/s41593-019-0556-3
State	Published - Jan 1 2020
Externally published	Yes

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© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

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Graves, S. M., Xie, Z., Stout, K. A., Zampese, E., Burbulla, L. F., Shih, J. C., Kondapalli, J., Patriarchi, T., Tian, L., Brichta, L., Greengard, P., Krainc, D., Schumacker, P. T., & Surmeier, D. J. (2020). Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain. Nature neuroscience, 23(1), 15-20. https://doi.org/10.1038/s41593-019-0556-3

Graves, SM, Xie, Z, Stout, KA, Zampese, E, Burbulla, LF, Shih, JC, Kondapalli, J, Patriarchi, T, Tian, L, Brichta, L, Greengard, P, Krainc, D, Schumacker, PT & Surmeier, DJ 2020, 'Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain', Nature neuroscience, vol. 23, no. 1, pp. 15-20. https://doi.org/10.1038/s41593-019-0556-3

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Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain

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