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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.* ; Taylor, R.W.* ; Prokisch, H. ; Kim, J.P.* ; Coon, J.J.* ; Pagliarini, D.J.*

Mitochondrial protein interaction mapping identifies regulators of respiratory chain function.

Mol. Cell 63, 621-632 (2016)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Green
Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal 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 mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter C15orf48 ; C2orf47 ; Dhrs4; Electron-transfer Flavoprotein; Coenzyme-q Biosynthesis; Yeast Mitochondria; Assembly Factor; Complex; Mutations; Quantification; Deficiency; Disorders; Disease
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1097-2765
e-ISSN 1097-4164
Zeitschrift Molecular Cell
Quellenangaben Band: 63, Heft: 4, Seiten: 621-632 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Cambridge
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
DOI 10.1016/j.molcel.2016.06.033
WOS ID WOS:000381620300010
Scopus ID 84992735863
PubMed ID 27499296
Erfassungsdatum 2016-08-10
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