Miklovicova 2024 Biochim Biophys Acta Mol Basis Dis
| Miklovicova S, Volpini L, Sanovec O, Monaco F, Vanova KH, Novak J, Boukalova S, Zobalova R, Klezl P, Tomasetti M, Bobek V, Fiala V, Vcelak J, Santarelli L, Bielcikova Z, Komrskova K, Kolostova K, Pacak K, Dvorakova S, Neuzil J (2024) Mitochondrial respiratory complex II is altered in renal carcinoma. Biochim Biophys Acta Mol Basis Dis 1871:167556. https://doi.org/10.1016/j.bbadis.2024.167556 |
Miklovicova Sona, Volpini Luca, Sanovec Ondrej, Monaco Federica, Vanova Katerina Hadrava, Novak Jaromir, Boukalova Stepana, Zobalova Renata, Klezl Petr, Tomasetti Marco, Bobek Vladimir, Fiala Vojtech, Vcelak Josef, Santarelli Lory, Bielcikova Zuzana, Komrskova Katerina, Kolostova Katarina, Pacak Karel, Dvorakova Sarka, Neuzil Jiri (2024) Biochim Biophys Acta Mol Basis Dis
Abstract: 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.
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.
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.
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. • Keywords: Complex II, Metabolism, Mitochondria, Organoids, Renal cell carcinoma, Succinate dehydrogenase • Bioblast editor: Plangger M • O2k-Network Lab: CZ Prague Neuzil J
Labels: MiParea: Respiration, nDNA;cell genetics, Patients
Pathology: Cancer
Organism: Human Tissue;cell: Kidney Preparation: Homogenate
Coupling state: OXPHOS
Pathway: S, CIV, ROX
HRR: Oxygraph-2k
2024-11
