Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function

作者：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^*

来源：Molecular Cell, 2016, 63(4): 621-632.

DOI：10.1016/j.molcel.2016.06.033

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.

• 出版日期2016-8-18