Mitochondrial respiratory complex II is altered in renal carcinoma

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-10-31 DOI:10.1016/j.bbadis.2024.167556

Sona Miklovicova , Luca Volpini , Ondrej Sanovec , Federica Monaco , Katerina Hadrava Vanova , Jaromir Novak , Stepana Boukalova , Renata Zobalova , Petr Klezl , Marco Tomasetti , Vladimir Bobek , Vojtech Fiala , Josef Vcelak , Lory Santarelli , Zuzana Bielcikova , Katerina Komrskova , Katarina Kolostova , Karel Pacak , Sarka Dvorakova , Jiri Neuzil

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引用次数: 0

Abstract

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.

Abstract Image

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肾癌的线粒体呼吸复合体 II 发生了改变。

背景：肾细胞癌（RCC）是一种以细胞代谢异常为特征的疾病。线粒体的功能，包括线粒体呼吸复合体 II（CII）亚基，尤其是 SDHB，经常受到影响。在此，我们研究了 RCC 患者体内 CII 的状态和功能：方法：我们对 78 名不同组织类型的 RCC 患者的肿瘤组织和邻近的健康肾脏组织进行了评估，重点研究了它们的线粒体功能。由于透明细胞 RCC（ccRCC）是迄今为止最常见的 RCC 组织类型，因此我们重点研究了这些患者，并根据病理 WHO/ISUP 分级系统将其分为低分级和高级别患者，以反映预后情况。结果：ccRCC肿瘤的特点是von Hippel-Lindau基因突变和碳酸酐酶IX的高表达。我们在 ccRCC 肿瘤组织中发现线粒体 DNA、蛋白质和功能以及 CII 功能水平较低，而在其他 RCC 类型和非肿瘤组织中则没有发现。高级别肿瘤中线粒体含量增加，而CII的功能仍然很低。ccRCC患者的肿瘤组织细胞再现了RCC组织的分子特征：我们的研究结果表明，随着ccRCC病情的逐渐严重，CII的状态（以其组装和SDHB水平为缩影）会恶化。这些观察结果有望对预后较差的患者进行分层，并为探索有针对性的治疗干预措施提供指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.