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Mitochondrial respiratory complex II is altered in renal carcinoma

S. Miklovicova, L. Volpini, O. Sanovec, F. Monaco, KH. Vanova, J. Novak, S. Boukalova, R. Zobalova, P. Klezl, M. Tomasetti, V. Bobek, V. Fiala, J. Vcelak, L. Santarelli, Z. Bielcikova, K. Komrskova, K. Kolostova, K. Pacak, S. Dvorakova, J. Neuzil

. 2025 ; 1871 (1) : 167556. [pub] 20241031

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc25002887

BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.

Citace poskytuje Crossref.org

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$a BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.
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$a Volpini, Luca $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy
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$a Sanovec, Ondrej $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech Republic
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$a Monaco, Federica $u Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy
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$a Vanova, Katerina Hadrava $u Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
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$a Novak, Jaromir $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech Republic
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$a Boukalova, Stepana $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic
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$a Zobalova, Renata $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic
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$a Klezl, Petr $u General University Hospital Kralovske Vinohrady, 100 34 Prague, Czech Republic
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$a Tomasetti, Marco $u Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy
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$a Bobek, Vladimir $u General University Hospital Kralovske Vinohrady, 100 34 Prague, Czech Republic; Department of Thoracic Surgery, Krajska zdravotni a.s. and UJEP, 400 11 Usti and Labem, Czech Republic; Department of Thoracic Surgery, Faculty of Medicine, Wroclaw University of Science and Technology, 51 377 Wroclaw, Poland
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$a Fiala, Vojtech $u General University Hospital, 128 08 Prague, Czech Republic
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$a Vcelak, Josef $u Department of Molecular Endocrinology, Institute of Endocrinology, 110 00 Prague, Czech Republic
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$a Santarelli, Lory $u Department of Clinical and Molecular Sciences, Polytechnic University of Marche, 60126 Ancona, Italy
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$a Bielcikova, Zuzana $u General University Hospital, 128 08 Prague, Czech Republic
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$a Komrskova, Katerina $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech Republic
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$a Kolostova, Katarina $u General University Hospital Kralovske Vinohrady, 100 34 Prague, Czech Republic
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$a Pacak, Karel $u Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA
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$a Dvorakova, Sarka $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic. Electronic address: sarka.dvorakova@ibt.cas.cz
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$a Neuzil, Jiri $u Institute of Biotechnology, Czech Academy of Sciences, 252 50 Prague-West, Czech Republic; Faculty of Science, Charles University, 128 00 Prague, Czech Republic; School of Pharmacy and Medical Science, Griffith University, Southport, Qld 4222, Australia; First Faculty of Medicine, Charles University, 121 08 Prague, Czech Republic. Electronic address: j.neuzil@griffith.edu.au
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