MICU2 up-regulation enhances tumor aggressiveness and metabolic reprogramming during colorectal cancer development
The mitochondrial Ca2+ uniporter (MCU) plays crucial role in intramitochondrial Ca2+ uptake, allowing Ca2+-dependent activation of oxidative metabolism. In recent decades, the role of MCU pore-forming proteins has been highlighted in cancer. However, the contribution of MCU-associated regulatory proteins mitochondrial calcium uptake 1 and 2 (MICU1 and MICU2) to pathophysiological conditions has been poorly investigated. Here, we describe the role of MICU2 in cell proliferation and invasion using in vitro and in vivo models of human colorectal cancer (CRC). Transcriptomic analysis demonstrated an increase in MICU2 expression and the MICU2/MICU1 ratio in advanced CRC and CRC-derived metastases. We report that expression of MICU2 is necessary for mitochondrial Ca2+ uptake and quality of the mitochondrial network. Our data reveal the interplay between MICU2 and MICU1 in the metabolic flexibility between anaerobic glycolysis and OXPHOS. Overall, our study sheds light on the potential role of the MICUs in diseases associated with metabolic reprogramming.
Authors
- Stéphanie Chadet (ORCID: https://orcid.org/0000-0001-7383-8232)
- William Raoul (ORCID: https://orcid.org/0000-0002-5040-3372)
- Stéphane Servais (ORCID: https://orcid.org/0000-0002-3127-9679)
- Naïg Guéguen (ORCID: https://orcid.org/0000-0002-3094-8121)
- Christophe Vandier (ORCID: https://orcid.org/0000-0003-2559-0660)
- Olivier Hérault (ORCID: https://orcid.org/0000-0002-7419-1124)
- David Crottès (ORCID: https://orcid.org/0000-0002-4038-6345)
- Isabelle Domingo
- Arnaud Chevrollier (ORCID: https://orcid.org/0000-0002-5135-6643)
- Jean‐François Dumas (ORCID: https://orcid.org/0000-0002-2293-6606)
- Thierry Lecomte (ORCID: https://orcid.org/0000-0001-5093-0212)
- Julien Sobilo (ORCID: https://orcid.org/0000-0003-4284-7552)
- Maxime Guéguinou (ORCID: https://orcid.org/0000-0002-5793-2082)
- Jérôme Bourgeais (ORCID: https://orcid.org/0000-0002-2557-9624)
- Alison Robert
Institutions
- Université de Tours (FR)
- Centre National de la Recherche Scientifique (FR)
- Transgene (France) (FR)
- Inserm (FR)
- Foie, Métabolisme, Cancer (FR)
- Université d'Angers (FR)
Publication Details
- Journal
- PLoS Biology
- Published
- 2024-10-28
- DOI
- https://doi.org/10.1371/journal.pbio.3002854
- Citations
- 3
- Primary Topic
- Cancer, Hypoxia, and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 0.86
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation ARC pour la Recherche sur le Cancer
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Institut National Du Cancer
- Studium Loire Valley-Institute for Advanced Studies
- PHENOMIN