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Deficiency of the complex I of the mitochondrial respiratory chain but improved adenylate control over succinate-dependent respiration are human gastric cancer-specific phenomena

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Abstract

The purpose of study was to comparatively characterize the oxidative phosphorylation (OXPHOS) and function of respiratory chain in mitochondria in human gastric corpus mucosa undergoing transition from normal to cancer states and in human gastric cancer cell lines, MKN28 and MKN45. The tissue samples taken by endobiopsy and the cells were permeabilized by saponin treatment to assess mitochondrial function in situ by high-resolution oxygraphy. Compared to the control group of endobiopsy samples, the maximal capacity of OXPHOS in the cancer group was almost twice lower. The respiratory chain complex I-dependent respiration, normalized to complex II-dependent respiration, was reduced that suggests deficiency of complex I, but the respiratory control by ADP in the presence of succinate was increased. Similar changes were observed also in mucosa adjacent to cancer tissue. The respiratory capacity of MKN45 cells was higher than that of MKN28 cells, but both types of cells exhibited a deficiency of complex I of the respiratory chain which appears to be an intrinsic property of the cancer cells. In conclusion, human gastric cancer is associated with decreased respiratory capacity, deficiency of the respiratory complex I of mitochondria, and improved coupling of succinate oxidation to phosphorylation in tumor tissue and adjacent atrophic mucosa. Detection of these changes in endobiopsy samples may be of diagnostic value.

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Acknowledgments

This study was supported by Grant no. 7117 of the Estonian Science Foundation and Grant 0182549s03 of the Estonian Ministry of Education and Research. The authors thank Mrs Ellen Gvozdkova for technical assistance. A.H. is K. Albin Johansson Research Professor of the Foundation for the Finnish Cancer Institute.

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Authors and Affiliations

  1. Department of Pathophysiology, Institute of General and Molecular Pathology, Faculty of Medicine, University of Tartu, 19 Ravila Street, 50411, Tartu, Estonia

    Marju Puurand, Nadežda Peet & Enn Seppet

  2. Department of Surgery, Faculty of Medicine, University of Tartu, Tartu, Estonia

    Marju Puurand, Margot Peetsalu & Ants Peetsalu

  3. Department of Human Biology and Genetics, Institute of General and Molecular Pathology, Faculty of Medicine, University of Tartu, Tartu, Estonia

    Andres Piirsoo

  4. Department of Haematology and Oncology, Faculty of Medicine, University of Tartu, Tartu, Estonia

    Jaan Soplepmann

  5. Department of Pathology, Tartu University Hospital, Tartu, Estonia

    Meeli Sirotkina

  6. Cancer Gene Therapy Group, Molecular Cancer Biology Program, Transplantation Laboratory, Haartman Institute and Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland

    Akseli Hemminki

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  1. Marju Puurand
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Puurand, M., Peet, N., Piirsoo, A. et al. Deficiency of the complex I of the mitochondrial respiratory chain but improved adenylate control over succinate-dependent respiration are human gastric cancer-specific phenomena. Mol Cell Biochem 370, 69–78 (2012). https://doi.org/10.1007/s11010-012-1399-3

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