Journal
MOLECULAR CELL
Volume 63, Issue 4, Pages 621-632Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2016.06.033
Keywords
-
Categories
Funding
- Searle Scholars Award
- NIH [U01GM94622, R01DK098672, R01GM112057, R01GM115591, R35GM118110, R01GM029076, T32DK007665, T32GM008692 MSTP, T15LM007359, T32HL007899, F30AG043282, T32GM07215]
- Wisconsin Distinguished Graduate Fellowship
- NSF
- Wellcome Trust [096919/Z/11/Z]
- MRC Centre for Neuromuscular Diseases [G0601943]
- UK NHS Highly Specialised Rare Mitochondrial Disorders of Adults and Children Service
- Lily Foundation
- National Institute for Health Research (NIHR) [NIHR-HCS-D12-03-04]
- German Bundesministerium fur Bildung und Forschung (BMBF) through the German Network for mitochondrial disorders (mitoNET) [01GM1113C]
- E-Rare project GENOMIT [01GM1603]
- EC FP7-PEOPLE-ITN Mitochondrial European Educational Training Project (GA) [317433]
- EU [633974]
- Medical Research Council [G0601943] Funding Source: researchfish
- National Institute for Health Research [NIHR-HCS-D12-03-04] Funding Source: researchfish
- MRC [G0601943] Funding Source: UKRI
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available