Faculty Collaboration Database

Mitochondrial proteome analysis reveals that an augmented cytochrome c oxidase assembly and activity potentiates respiratory capacity in sarcoma. Biochem Biophys Res Commun 2024 Dec 03;736:150501

Date

08/09/2024

Pubmed ID

39116681

DOI

10.1016/j.bbrc.2024.150501

Scopus ID

2-s2.0-85200872122 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

Mitochondrial oxidative phosphorylation (OXPHOS) is an obligatory process in sarcoma. Despite that, the metabolic programming of sarcoma mitochondria is still unknown. To obtain a comprehensive metabolic insight of mitochondria, we developed a mouse fibrosarcoma model by injecting 3-methylcholanthrene and compared mitochondrial proteomes between sarcoma and its contralateral normal muscle using mass spectrometry. Our study identified ∼449 proteins listed in the SwissProt databases, and all the data sets are available via ProteomeXchange with the identifier PXD044903. In sarcoma, 49 mitochondrial proteins were found differentially expressed, including 36 proteins up-regulated and 13 proteins down-regulated, with the significance of p-value <0.05 and the log₂[fold change] > 1 and < -1 as compared to normal muscle. Our data revealed that various anaplerotic reactions actively replenish the TCA cycle in sarcoma. The comparative expression profile and Western blotting analysis of OXPHOS subunits showed that complex-IV subunits, MT-CO3 and COX6A1, were significantly up-regulated in sarcoma vs. normal muscle. Further, biochemical and physiological assays confirmed enhanced complex-IV specific enzymatic and supercomplex activities with a concomitant increase of oxygen consumption rate in sarcoma mitochondria compared to normal muscle. Validation with human post-operative sarcoma tissues also confirms an increased MT-CO3 expression compared to normal tissue counterparts. Thus, our data comprehensively analyses the mitochondrial proteome and identifies augmented complex-IV assembly and activity in sarcoma.

Author List

Bedi M, Das S, Das J, Mukherjee S, Basu A, Saha S, Ghosh A

Author

Manpreet Bedi MD, MS Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Respiration
Electron Transport Complex IV
Fibrosarcoma
Male
Mice
Mitochondria
Mitochondrial Proteins
Oxidative Phosphorylation
Oxygen Consumption
Proteome
Proteomics
Sarcoma