2. Academic Validation
  3. Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function

Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function

  • Mol Cell. 2016 Aug 18;63(4):621-632. doi: 10.1016/j.molcel.2016.06.033.
Brendan J Floyd 1,  Emily M Wilkerson 2,  Mike T Veling 1,  Catie E Minogue 2,  Chuanwu Xia 3,  Emily T Beebe 4,  Russell L Wrobel 4,  Holly Cho 1,  Laura S Kremer 5,  Charlotte L Alston 6,  Katarzyna A Gromek 4,  Brendan K Dolan 4,  Arne Ulbrich 2,  Jonathan A Stefely 1,  Sarah L Bohl 1,  Kelly M Werner 4,  Adam Jochem 7,  Michael S Westphall 8,  Jarred W Rensvold 7,  Robert W Taylor 6,  Holger Prokisch 5,  Jung-Ja P Kim 3,  Joshua J Coon 9,  David J Pagliarini 10
Affiliations

Affiliations

  • 1 Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • 2 Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • 3 Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • 4 Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • 5 Institute of Human Genetics, Technische Universität München, 81675 München, Germany; Institute of Human Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
  • 6 Wellcome Trust Centre for Mitochondrial Research, Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • 7 Morgridge Institute for Research, Madison, WI 53715, USA.
  • 8 Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • 9 Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA; Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • 10 Morgridge Institute for Research, Madison, WI 53715, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address: dpagliarini@morgridge.org.
PMID: 27499296 DOI: 10.1016/j.molcel.2016.06.033
Abstract

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.

Keywords

C15orf48; C2orf47; DHRS4.

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