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Mitochondrial Proteins as Exosomal Cargo: New Breast Cancer Biomarkers & Crucial Players in Carcinogenesis? Full article

Journal Molecules
ISSN: 1420-3049
Output data Year: 2025, Volume: 30, Number: 20, Article number : 4112, Pages count : 15 DOI: 10.3390/molecules30204112
Authors Shefer Aleksei 1 , Yanshole Lyudmila 1 , Grygor’eva Alina 1 , Yunusova Natalia 2,3 , Kondakova Irina 2 , Spirina Liudmila 3 , Shevela Andrey 1 , Chernyshova Alyona 1 , Romanov Alexander 4,5 , Tamkovich Svetlana 1
Affiliations
1 Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia
2 Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, Russia
3 Department of Biochemistry and Molecular Biology with a Course in Clinical Laboratory Diagnostics, Siberian State Medical University, 634050 Tomsk, Russia
4 Cardiovascular Surgery Department, Novosibirsk State Medical University, 630091 Novosibirsk, Russia
5 E.N. Meshalkin National Medical Research Center, Ministry of Health of the Russian Federation, 630055 Novosibirsk, Russia

Abstract: Mitochondrial proteins (mtPs) packaged into extracellular vesicles (EVs), particularly exosomes, have emerged as promising biomarkers and functional mediators in cancer biology. In this study, we investigated whether breast cancer (BC)-derived exosomes selectively incorporate mtPs, thereby providing insights into their diagnostic potential and role in tumor progression. Exosomes were isolated from conditioned media of multiple BC cell lines and non-tumorigenic breast epithelial cells using ultracentrifugation and were characterized by transmission electron microscopy and flow cytometry for canonical markers CD9 and CD81. Proteomic profiling by MALDI-TOF mass spectrometry revealed a distinct enrichment of mtPs in exosomes derived exclusively from tumor cells, while non-tumorigenic cells lacked such cargo. Identified proteins were predominantly associated with the oxidative phosphorylation system, with Complex I subunits most frequently detected, whereas Complex II components were entirely absent. These findings highlight a cancer-specific mechanism of exosomal mtP incorporation, potentially reflecting altered energy metabolism and stress responses in malignant cells. We conclude that mtPs in exosomes represent both functional contributors to tumor progression and promising candidates for liquid biopsy-based BC diagnostics.
Cite: Shefer A. , Yanshole L. , Grygor’eva A. , Yunusova N. , Kondakova I. , Spirina L. , Shevela A. , Chernyshova A. , Romanov A. , Tamkovich S.
Mitochondrial Proteins as Exosomal Cargo: New Breast Cancer Biomarkers & Crucial Players in Carcinogenesis?
Molecules. 2025. V.30. N20. 4112 :1-15. DOI: 10.3390/molecules30204112
Dates:
Submitted: Sep 16, 2025
Accepted: Oct 14, 2025
Published online: Oct 16, 2025
Identifiers: No identifiers
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