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Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function

Open access
Floyd, Brendan J., Wilkerson, Emily M., Veling, Mike T., Minogue, Catie E., Xia, Chuanwu, Beebe, Emily T., Wrobel, Russell L., Cho, Holly, Kremer, Laura S., Alston, Charlotte L., Gromek, Katarzyna A., Dolan, Brendan K., Ulbrich, Arne, Stefely, Jonathan A., Bohl, Sarah L., Werner, Kelly M., Jochem, Adam, Westphall, Michael S., Rensvold, Jarred W., Taylor, Robert W., Prokisch, Holger, Kim, Jung-Ja P., Coon, Joshua J., Pagliarini, David J.·2016·Molecular Cell

Abstract

SUMMARY Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal new functions for these proteins (termed MXPs) we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend new mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function.

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Metadata

Authors
Floyd, B. J., Wilkerson, E. M., Veling, M. T., Minogue, C. E., Xia, C., Beebe, E. T., Wrobel, R. L., Cho, H., Kremer, L. S., Alston, C. L., Gromek, K. A., Dolan, B. K., Ulbrich, A., Stefely, J. A., Bohl, S. L., Werner, K. M., Jochem, A., Westphall, M. S., Rensvold, J. W., Taylor, R. W., Prokisch, H., Kim, J.-J. P., Coon, J. J., & Pagliarini, D. J.
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2016-08
Volume
63
Issue
4
Pages
621-632
ISSN
1097-2765 (ISSN-L)
OpenAlex
W2492521149
Cited by
264
References
9
FWCI
15.35
Type
journal article
Language
en
Open access
bronze

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Floyd, B. J., Wilkerson, E. M., Veling, M. T., Minogue, C. E., Xia, C., Beebe, E. T., Wrobel, R. L., Cho, H., Kremer, L. S., Alston, C. L., Gromek, K. A., Dolan, B. K., Ulbrich, A., Stefely, J. A., Bohl, S. L., Werner, K. M., Jochem, A., Westphall, M. S., Rensvold, J. W., . . . Pagliarini, D. J. (2016). Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function. Molecular Cell. https://doi.org/10.1016/j.molcel.2016.06.033

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.