Mitochondrial respiratory complex II is altered in renal carcinoma
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
39486656
DOI
10.1016/j.bbadis.2024.167556
PII: S0925-4439(24)00550-7
Knihovny.cz E-zdroje
- Klíčová slova
- Complex II, Metabolism, Mitochondria, Organoids, Renal cell carcinoma, Succinate dehydrogenase,
- MeSH
- antigeny nádorové MeSH
- dospělí MeSH
- karboanhydrasa IX metabolismus genetika MeSH
- karcinom z renálních buněk * patologie metabolismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mitochondriální DNA genetika metabolismus MeSH
- mitochondrie * metabolismus patologie genetika MeSH
- mutace MeSH
- nádorový supresorový protein VHL genetika metabolismus MeSH
- nádory ledvin * patologie metabolismus genetika MeSH
- respirační komplex II * metabolismus genetika MeSH
- senioři MeSH
- sukcinátdehydrogenasa genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny nádorové MeSH
- CA9 protein, human MeSH Prohlížeč
- karboanhydrasa IX MeSH
- mitochondriální DNA MeSH
- nádorový supresorový protein VHL MeSH
- respirační komplex II * MeSH
- respiratory complex II MeSH Prohlížeč
- SDHB protein, human MeSH Prohlížeč
- sukcinátdehydrogenasa MeSH
- VHL protein, human MeSH Prohlížeč
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.
Department of Clinical and Molecular Sciences Polytechnic University of Marche 60126 Ancona Italy
Department of Molecular Endocrinology Institute of Endocrinology 110 00 Prague Czech Republic
General University Hospital 128 08 Prague Czech Republic
General University Hospital Kralovske Vinohrady 100 34 Prague Czech Republic
Institute of Biotechnology Czech Academy of Sciences 252 50 Prague West Czech Republic
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