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Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning

Metabolic reprogramming is a hallmark of cancer. Such reprogramming entails the up-regulation of the expression of specific mitochondrial proteins, thus increasing the burden on the mitochondrial protein quality control. However, very little is known about the specificity of interactions between mit...

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Autores principales: Galai, Geut, Ben-David, Hila, Levin, Liron, Orth, Martin F., Grünewald, Thomas G. P., Pilosof, Shai, Bershtein, Shimon, Rotblat, Barak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226338/
https://www.ncbi.nlm.nih.gov/pubmed/32235444
http://dx.doi.org/10.3390/cancers12040825
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author Galai, Geut
Ben-David, Hila
Levin, Liron
Orth, Martin F.
Grünewald, Thomas G. P.
Pilosof, Shai
Bershtein, Shimon
Rotblat, Barak
author_facet Galai, Geut
Ben-David, Hila
Levin, Liron
Orth, Martin F.
Grünewald, Thomas G. P.
Pilosof, Shai
Bershtein, Shimon
Rotblat, Barak
author_sort Galai, Geut
collection PubMed
description Metabolic reprogramming is a hallmark of cancer. Such reprogramming entails the up-regulation of the expression of specific mitochondrial proteins, thus increasing the burden on the mitochondrial protein quality control. However, very little is known about the specificity of interactions between mitochondrial chaperones and their clients, or to what extent the mitochondrial chaperone–client co-expression is coordinated. We hypothesized that a physical interaction between a chaperone and its client in mitochondria ought to be manifested in the co-expression pattern of both transcripts. Using The Cancer Genome Atlas (TCGA) gene expression data from 13 tumor entities, we constructed the mitochondrial chaperone-client co-expression network. We determined that the network is comprised of three distinct modules, each populated with unique chaperone-clients co-expression pairs belonging to distinct functional groups. Surprisingly, chaperonins HSPD1 and HSPE1, which are known to comprise a functional complex, each occupied a different module: HSPD1 co-expressed with tricarboxylic acid cycle cycle enzymes, while HSPE1 co-expressed with proteins involved in oxidative phosphorylation. Importantly, we found that the genes in each module were enriched for discrete transcription factor binding sites, suggesting the mechanism for the coordinated co-expression. We propose that our mitochondrial chaperone–client interactome can facilitate the identification of chaperones supporting specific mitochondrial pathways and bring forth a fundamental principle in metabolic adaptation.
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spelling pubmed-72263382020-05-18 Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning Galai, Geut Ben-David, Hila Levin, Liron Orth, Martin F. Grünewald, Thomas G. P. Pilosof, Shai Bershtein, Shimon Rotblat, Barak Cancers (Basel) Article Metabolic reprogramming is a hallmark of cancer. Such reprogramming entails the up-regulation of the expression of specific mitochondrial proteins, thus increasing the burden on the mitochondrial protein quality control. However, very little is known about the specificity of interactions between mitochondrial chaperones and their clients, or to what extent the mitochondrial chaperone–client co-expression is coordinated. We hypothesized that a physical interaction between a chaperone and its client in mitochondria ought to be manifested in the co-expression pattern of both transcripts. Using The Cancer Genome Atlas (TCGA) gene expression data from 13 tumor entities, we constructed the mitochondrial chaperone-client co-expression network. We determined that the network is comprised of three distinct modules, each populated with unique chaperone-clients co-expression pairs belonging to distinct functional groups. Surprisingly, chaperonins HSPD1 and HSPE1, which are known to comprise a functional complex, each occupied a different module: HSPD1 co-expressed with tricarboxylic acid cycle cycle enzymes, while HSPE1 co-expressed with proteins involved in oxidative phosphorylation. Importantly, we found that the genes in each module were enriched for discrete transcription factor binding sites, suggesting the mechanism for the coordinated co-expression. We propose that our mitochondrial chaperone–client interactome can facilitate the identification of chaperones supporting specific mitochondrial pathways and bring forth a fundamental principle in metabolic adaptation. MDPI 2020-03-30 /pmc/articles/PMC7226338/ /pubmed/32235444 http://dx.doi.org/10.3390/cancers12040825 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Galai, Geut
Ben-David, Hila
Levin, Liron
Orth, Martin F.
Grünewald, Thomas G. P.
Pilosof, Shai
Bershtein, Shimon
Rotblat, Barak
Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning
title Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning
title_full Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning
title_fullStr Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning
title_full_unstemmed Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning
title_short Pan-Cancer Analysis of Mitochondria Chaperone-Client Co-Expression Reveals Chaperone Functional Partitioning
title_sort pan-cancer analysis of mitochondria chaperone-client co-expression reveals chaperone functional partitioning
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226338/
https://www.ncbi.nlm.nih.gov/pubmed/32235444
http://dx.doi.org/10.3390/cancers12040825
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