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Mitochondrial protein functions elucidated by multi-omic mass spectrometry profiling

Journal Article · · Nature Biotechnology
DOI:https://doi.org/10.1038/nbt.3683· OSTI ID:1463133
 [1];  [2];  [2];  [2];  [3];  [2];  [2];  [4];  [2];  [4];  [4];  [4];  [2];  [2];  [4];  [5];  [5];  [5];  [4];  [2]
  1. Univ. of Wisconsin, Madison, WI (United States); Morgridge Inst. for Research, Madison, WI (United States); OSTI
  2. Univ. of Wisconsin, Madison, WI (United States); Genome Center of Wisconsin, Madison, WI (United States)
  3. Morgridge Inst. for Research, Madison, WI (United States)
  4. Univ. of Wisconsin, Madison, WI (United States); Morgridge Inst. for Research, Madison, WI (United States)
  5. Genome Center of Wisconsin, Madison, WI (United States)
Mitochondrial dysfunction is associated with many human diseases, including cancer and neurodegeneration, that are often linked to proteins and pathways that are not well-characterized. To begin defining the functions of such poorly characterized proteins, we used mass spectrometry to map the proteomes, lipidomes and metabolomes of 174 yeast strains, each lacking a single gene related to mitochondrial biology. 144 of these genes have human homologs, 60 of which are associated with disease and 39 of which are uncharacterized. We present a multi-omic data analysis and visualization tool that we use to find covariance networks that can predict molecular functions, correlations between profiles of related gene deletions, gene-specific perturbations that reflect protein functions, and a global respiration deficiency response. Using this multi-omic approach, we link seven proteins including Hfd1p and its human homolog ALDH3A1 to mitochondrial coenzyme Q (CoQ) biosynthesis, an essential pathway disrupted in many human diseases. This Resource should provide broad molecular insights into mitochondrial protein functions.
Research Organization:
Univ. of Wisconsin, Madison, WI (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
FC02-07ER64494
OSTI ID:
1463133
Journal Information:
Nature Biotechnology, Journal Name: Nature Biotechnology Journal Issue: 11 Vol. 34; ISSN 1087-0156
Publisher:
Springer NatureCopyright Statement
Country of Publication:
United States
Language:
English

References (53)

Coenzyme Q and mitochondrial disease journal June 2010
Age-related changes in the lipid compositions of rat and human tissues journal July 1989
The Mitochondrial Proteome: From Inventory to Function journal July 2008
Mitochondria: In Sickness and in Health journal March 2012
News in Ubiquinone Biosynthesis journal May 2010
The Sjögren-Larsson Syndrome Gene Encodes a Hexadecenal Dehydrogenase of the Sphingosine 1-Phosphate Degradation Pathway journal May 2012
Functional Discovery via a Compendium of Expression Profiles journal July 2000
Development of a GC/Quadrupole-Orbitrap Mass Spectrometer, Part I: Design and Characterization journal September 2014
Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment journal April 2011
Charting a course for genomic medicine from base pairs to bedside journal February 2011
Mitochondrial disorders as windows into an ancient organelle journal November 2012
Defining the consequences of genetic variation on a proteome-wide scale journal June 2016
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification journal November 2008
Sjögren–Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene journal January 1996
Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A journal April 2004
Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry journal February 2007
One-hour proteome analysis in yeast journal April 2015
Phenotypic and genetic variance: a systems approach to the liver journal June 2016
The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold journal April 1997
Monogenic Mitochondrial Disorders journal March 2012
The proteome of Saccharomyces cerevisiae mitochondria journal October 2003
para -Aminobenzoic Acid Is a Precursor in Coenzyme Q 6 Biosynthesis in Saccharomyces cerevisiae journal June 2010
The One Hour Yeast Proteome journal October 2013
Mitofusin 2 is required to maintain mitochondrial coenzyme Q levels journal February 2015
Clustal W and Clustal X version 2.0 journal September 2007
Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy journal April 2011
MitoCarta2.0: an updated inventory of mammalian mitochondrial proteins journal October 2015
Hallmarks of a new era in mitochondrial biochemistry journal December 2013
Global Network Reorganization During Dynamic Adaptations of Bacillus subtilis Metabolism journal March 2012
Update on the aldehyde dehydrogenase gene (ALDH) superfamily journal January 2011
Age-related changes in the lipid compositions of rat and human tissues journal July 1989
In-frame deletion in canine PITRM1 is associated with a severe early-onset epilepsy, mitochondrial dysfunction and neurodegeneration journal April 2021
The origin of the benzoquinone ring of coenzyme Q9 in the rat journal September 1961
Urinary Phenolic Acid Metabolites of Tyrosine journal September 1960
Functional Discovery via a Compendium of Expression Profiles journal July 2000
Substrate specificity, plasma membrane localization, and lipid modification of the aldehyde dehydrogenase ALDH3B1 journal August 2013
The molecular genetics of coenzyme Q biosynthesis in health and disease journal May 2014
A Mitochondrial Protein Compendium Elucidates Complex I Disease Biology journal July 2008
Large-Scale Genetic Perturbations Reveal Regulatory Networks and an Abundance of Gene-Specific Repressors journal April 2014
Involvement of Mitochondrial Ferredoxin and Para-Aminobenzoic Acid in Yeast Coenzyme Q Biosynthesis journal May 2010
Endogenous synthesis of coenzyme Q in eukaryotes journal June 2007
Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function journal August 2016
Functional profiling of the Saccharomyces cerevisiae genome journal July 2002
Monogenic Mitochondrial Disorders journal March 2012
para -Aminobenzoic Acid Is a Precursor in Coenzyme Q 6 Biosynthesis in Saccharomyces cerevisiae journal June 2010
Amine-reactive Neutron-encoded Labels for Highly Plexed Proteomic Quantitation journal July 2013
The One Hour Yeast Proteome journal October 2013
MUSCLE: multiple sequence alignment with high accuracy and high throughput journal March 2004
Multiple High-Throughput Analyses Monitor the Response of E. coli to Perturbations journal April 2007
Systems proteomics of liver mitochondria function journal June 2016
The S-Phase Cyclin Clb5 Promotes rRNA Gene (rDNA) Stability by Maintaining Replication Initiation Efficiency in rDNA journal April 2021
Complete Genome Sequence of Clostridium botulinum CJ0611A1, a Type A(B) Isolate Associated with an International Outbreak of Botulism from Commercial Carrot Juice journal January 2021
Systems proteomics of liver mitochondria function text January 2016

Cited By (26)

Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses journal March 2018
Definition of a High-Confidence Mitochondrial Proteome at Quantitative Scale journal June 2017
Genetic Regulation of Plasma Lipid Species and Their Association with Metabolic Phenotypes journal June 2018
Argonaut: A Web Platform for Collaborative Multi-omic Data Visualization and Exploration journal October 2020
Detection of dysregulated protein-association networks by high-throughput proteomics predicts cancer vulnerabilities journal September 2017
Landscape of submitochondrial protein distribution journal August 2017
Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc1 complex function journal March 2019
Implications of genetic variation of common Drug Metabolizing Enzymes and ABC Transporters among the Pakistani Population journal May 2019
Real-time health monitoring through urine metabolomics journal November 2019
Exploiting Interdata Relationships in Next-generation Proteomics Analysis journal May 2019
The interactome of intact mitochondria by cross-linking mass spectrometry provides evidence for coexisting respiratory supercomplexes journal December 2017
Coenzyme Q biosynthetic proteins assemble in a substrate-dependent manner into domains at ER–mitochondria contacts journal January 2019
MS-Helios: a Circos wrapper to visualize multi-omic datasets journal January 2019
Genomic Determinants of Protein Abundance Variation in Colorectal Cancer Cells text January 2017
Impact of Chemical Analogs of 4-Hydroxybenzoic Acid on Coenzyme Q Biosynthesis: From Inhibition to Bypass of Coenzyme Q Deficiency journal June 2017
A path to the powerhouse: systems-to-structure approaches for studying mitochondrial proteins: A Path to the Powerhouse: Systems-to-Structure Approaches journal May 2018
General and specialized tyrosine metabolism pathways in plants journal September 2019
Capturing site-specific heterogeneity with large-scale N-glycoproteome analysis journal March 2019
Mitochondrial proteins: from biogenesis to functional networks journal January 2019
The cellular economy of the Saccharomyces cerevisiae zinc proteome journal January 2018
A proteome-integrated, carbon source dependent genetic regulatory network in Saccharomyces cerevisiae journal January 2020
Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc 1 complex function journal June 2018
Capturing site-specific heterogeneity with large-scale N-glycoproteome analysis journal January 2019
Metabolic Remodeling during Biofilm Development of Bacillus subtilis journal May 2019
Vanillic Acid Restores Coenzyme Q Biosynthesis and ATP Production in Human Cells Lacking COQ6 journal July 2019
The AAA ATPase Afg1 preserves mitochondrial fidelity and cellular health by maintaining mitochondrial matrix proteostasis journal October 2018

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