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An image-based map of the human mitochondrial proteome
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. (Emma Lundberg)ORCID iD: 0000-0002-6368-6690
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. (Emma Lundberg)ORCID iD: 0000-0001-7034-0850
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Defining the human mitochondrial proteome is crucial to understand the mitochondria’s diverse functions and role in disease. Here, we present an image-based map of the human mitochondrial proteome containing 1,070 proteins, of which 376 have previously not been reported to localize to the mitochondria. Our analysis shows that approximately 50% (n=493) of the proteins localize to additional cellular compartments, likely contributing to the diverse cellular functions of mitochondria. This map of the mitochondrial proteome, part of the Cell Atlas of the Human Protein Atlas database (www.proteinatlas.org), provides a valuable knowledge resource for studies of mitochondria function, dysfunction and disease.

Keyword [en]
Mitochondria, Human Protein Atlas, Human Proteome, Immunofluorescence, Multilocalizing protein
National Category
Cell Biology
Research subject
Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-206811OAI: oai:DiVA.org:kth-206811DiVA: diva2:1093888
Funder
Knut and Alice Wallenberg Foundation
Note

QC 20170512

Available from: 2017-05-08 Created: 2017-05-08 Last updated: 2017-05-12Bibliographically approved
In thesis
1. Spatial proteome profiling of the compartments of the human cell using an antibody-based approach
Open this publication in new window or tab >>Spatial proteome profiling of the compartments of the human cell using an antibody-based approach
2017 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

The human cell is complex, with countless processes ongoing in parallel in specialized compartments, the organelles. Cells can be studied in vitro by using immortalized cell lines that represent cells in vivo to a varying degree. Gene expression varies between cell types and an average cell line expresses around 10,000-12,000 genes, as measured with RNA sequencing. These genes encode the cell’s proteome; the full set of proteins that perform functions in the cell. In paper I we show that RNA sequencing is a necessary tool for studying the proteome of the human cell.

By studying the proteome, and proteins’ localization in the cell, information can be assembled on how the cell functions. Image-based methods allow for detailed spatial resolution of protein localization as well as enable the study of temporal events. Visualization of a protein can be accomplished by using either a cell line that is transfected to express the protein with a fluorescent tag, or by targeting the protein with an affinity reagent such as an antibody. In paper II we present subcellular data for a majority of the human proteins, showing that there is a high degree of complexity in regard to where proteins localize in the cell.

Cellular energy is generated in the mitochondria, an important organelle that is also active in many other different functions. Today approximately only a third of the estimated mitochondrial proteome has been validated experimentally, indicating that there is much more to understand with regard to the functions of the mitochondria. In paper III we explore the mitochondrial proteome, based on the results of paper II. We also present a method for sublocalizing proteins to subcompartments that can be performed in a high-throughput manner.

To conclude, this thesis shows that transcriptomics is a useful tool for proteome-wide subcellular localization, and presents high-resolution spatial distribution data for the human cell with a deeper analysis of the mitochondrial proteome.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2017. 49 p.
Series
TRITA-BIO-Report, ISSN 1654-2312 ; 2017:11
Keyword
Fluorescence imaging, Human proteome, Human Protein Atlas, Immunofluorescence, Mitochondria, Organelles, Spatial distribution
National Category
Cell Biology
Research subject
Biotechnology
Identifiers
urn:nbn:se:kth:diva-206817 (URN)978-91-7729-393-4 (ISBN)
Presentation
2017-06-16, Gamma 2, Tomtebodavägen 23A, Solna, 10:00 (English)
Opponent
Supervisors
Funder
Knut and Alice Wallenberg Foundation
Note

QC 20170512

Available from: 2017-05-12 Created: 2017-05-12 Last updated: 2017-05-12Bibliographically approved

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