NMR-Based Mitochondria Metabolomic Profiling: A New Approach To Reveal Cancer-Associated Alterations.

Fecha de publicación: 14/11/2023 Fecha Ahead of Print: 01/10/2023

Autores de CIPF

Ana Armiñan De Benito

Autor
Maria Jesus Vicent Docon

Autor
Antonio Pineda Lucena

Autor
Martina Palomino Schatzlein

Autor

Participantes ajenos a CIPF

Domingo-Ortí I
Ferrer-Torres P

Grupos de Investigación

Laboratorio de Polímeros Terapéuticos

Jefe/a de Grupo

Maria Jesus Vicent Docon

Abstract

Studying metabolism may assist in understanding the relationship between normal and dysfunctional mitochondrial activity and various diseases, such as neurodegenerative, cardiovascular, autoimmune, psychiatric, and cancer. Nuclear magnetic resonance-based metabolomics represents a powerful method to characterize the chemical content of complex samples and has been successfully applied to studying a range of conditions. However, an optimized methodology is lacking for analyzing isolated organelles, such as mitochondria. In this study, we report the development of a protocol to metabolically profile mitochondria from healthy, tumoral, and metastatic tissues. Encouragingly, this approach provided quantitative information about up to 45 metabolites in one comprehensive and robust analysis. Our results revealed significant differences between whole-cell and mitochondrial metabolites, which supports a more refined approach to metabolic analysis. We applied our optimized methodology to investigate aggressive and metastatic breast cancer in mouse tissues, discovering that lung mitochondria exhibit an altered metabolic fingerprint. Specific amino acids, organic acids, and lipids showed significant increases in levels when compared with mitochondria from healthy tissues. Our optimized methodology could promote a better understanding of the molecular mechanisms underlying breast cancer aggressiveness and mitochondrial-related diseases and support the optimization of new advanced therapies.

Datos de la publicación

ISSN/ISSNe:: 0003-2700, 1520-6882
Tipo:: Article
Páginas:: 16539-16548
DOI:: 10.1021/acs.analchem.3c02432
PubMed:: 37906730

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Métricas

Filiaciones

Domingo-Ortí I:: Centro de Investigación Príncipe Felipe, Polymer Therapeutics Laboratory and CIBERONC, Valencia 46012, Spain

NMR Facility, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain

Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026, Spain
Ferrer-Torres P:: NMR Facility, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain
Armiñán A:: Centro de Investigación Príncipe Felipe, Polymer Therapeutics Laboratory and CIBERONC, Valencia 46012, Spain
Vicent MJ:: Centro de Investigación Príncipe Felipe, Polymer Therapeutics Laboratory and CIBERONC, Valencia 46012, Spain
Pineda-Lucena A:: Drug Discovery Unit, Instituto de Investigación Sanitaria La Fe, Valencia 46026, Spain

Molecular Therapeutics Program, CIMA Universidad de Navarra, Pamplona 31008, Spain
Palomino-Schätzlein M:: NMR Facility, Centro de Investigación Príncipe Felipe, Valencia 46012, Spain

ProtoQSAR, CEEI, Parque Tecnológico Valencia, Paterna 46980, Spain