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Article (Scientific journals)
Relevance of the TRIAP1/p53 axis in colon cancer cell proliferation and adaptation to glutamine deprivation
Nedara, Kenza; Reinhardt, Camille; Lebraud, Emilie et al.
2022In Frontiers in Oncology, 12 (958155)
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Keywords :
p53; TRIAP1; colon cancer; glutamine deprivation
Abstract :
[en] Human TRIAP1 (TP53-regulated inhibitor of apoptosis 1; also known as p53CSV for p53-inducible cell survival factor) is the homolog of yeast Mdm35, a well-known chaperone that interacts with the Ups/PRELI family proteins and participates in the intramitochondrial transfer of lipids for the synthesis of cardiolipin (CL) and phosphatidylethanolamine. Although recent reports indicate that TRIAP1 is a prosurvival factor abnormally overexpressed in various types of cancer, knowledge about its molecular and metabolic function in human cells is still elusive. It is therefore critical to understand the metabolic and proliferative advantages that TRIAP1 expression provides to cancer cells. Here, in a colorectal cancer cell model, we report that the expression of TRIAP1 supports cancer cell proliferation and tumorigenesis. Depletion of TRIAP1 perturbed the mitochondrial ultrastructure, without a major impact on CL levels and mitochondrial activity. TRIAP1 depletion caused extramitochondrial perturbations resulting in changes in the endoplasmic reticulum-dependent lipid homeostasis and induction of a p53-mediated stress response. Furthermore, we observed that TRIAP1 depletion conferred a robust p53-mediated resistance to the metabolic stress caused by glutamine deprivation. These findings highlight the importance of TRIAP1 in tumorigenesis and indicate that the loss of TRIAP1 has extramitochondrial consequences that could impact on the metabolic plasticity of cancer cells and their response to conditions of nutrient deprivation.
Disciplines :
Author, co-author :
Nedara, Kenza;  Université Paris-Saclay, CNRS > Gustave Roussy
Reinhardt, Camille;  Université Paris-Saclay, CNRS, > Gustave Roussy
Lebraud, Emilie;  Institut de Radioprotection et de Sûreté Nucléaire Laboratoire de radiobiologie des Expositions Médicales (IRSN), Fontenay-aux-Roses, France
Arena, Giuseppe ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience
Gracia, Céline
Buard, Valérie
Pioche-Durieu, Catherine
Castelli, Florence
Colsch, Benoit
Bénit, Paule
Rustin, Pierre
Albaud, Benoit
Gestraud, Pierre
Baulande, Sylvain
Servant, Nicolas
Deutsch, Eric
Verbavatz, Jean-Marc
Brenner, Catherine
Milliat, Fabien
Modjtahedi, Nazanine
More authors (10 more) Less
External co-authors :
Language :
Title :
Relevance of the TRIAP1/p53 axis in colon cancer cell proliferation and adaptation to glutamine deprivation
Publication date :
31 October 2022
Journal title :
Frontiers in Oncology
Publisher :
Frontiers Media, Lausanne, Switzerland
Volume :
Issue :
Peer reviewed :
Peer Reviewed verified by ORBi
FnR Project :
FNR15850547 > Giuseppe Arena > PINK1-DiaPDs > Pink1-related Molecular Mechanisms To Dissect The Connection Between Type 2 Diabetes And Insulin Resistance In Parkinson’S Disease > 01/01/2022 > 31/08/2024 > 2021


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