| Autor: |
Galai G; Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.; The National Institute for Biotechnology in the Negev, Beer Sheva 8410501, Israel., Ben-David H; Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.; The National Institute for Biotechnology in the Negev, Beer Sheva 8410501, Israel., Levin L; The National Institute for Biotechnology in the Negev, Beer Sheva 8410501, Israel., Orth MF; Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, 80337 Munich, Germany., Grünewald TGP; Max-Eder Research Group for Pediatric Sarcoma Biology, Institute of Pathology of the LMU Munich, 80337 Munich, Germany.; Institute of Pathology of the LMU Munich, 80337 Munich, Germany.; Division of Translational Pediatric Sarcoma Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Hopp Children's Cancer Center Heidelberg (KiTZ), 69120 Heidelberg, Germany.; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany., Pilosof S; Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel., Berstein S; Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel., Rotblat B; Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 8410501, Israel.; The National Institute for Biotechnology in the Negev, Beer Sheva 8410501, Israel. |
| Abstrakt: |
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. |
