Mitochondrial complex I is deficient in renal oncocytomas
Mitochondrial complex I is deficient in renal oncocytomas
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DOI：
10.1093/carcin/bgg109
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发表时间：
2003-09-01
期刊：
影响因子：
4.7
通讯作者：
Godinot, C
中科院分区：
文献类型：
--
作者：
Simonnet, H;Demont, J;Godinot, C
肾嗜酸细胞瘤是一种以线粒体密集堆积为特征的良性肿瘤，其病因至今不明。一致的是，线粒体DNA含量和几个氧化磷酸化（OXPHOS）复合物的量和催化活性已知在这些肿瘤中增加，但它不是确定的OXPHOS系统的功能。在这里，我们研究了线粒体复合物I，发现其NADH脱氢酶活性和蛋白质含量在嗜酸细胞瘤中特异性降低，与其他恶性肾肿瘤中所有呼吸链复合物的平行降低形成鲜明对比。我们的结论是，在嗜酸细胞瘤中复合物I的缺乏可能是导致线粒体生物合成增加的早期事件，试图弥补OXPHOS功能的丧失。由于其他肿瘤被发现与线粒体缺陷有关，如富马酸水合酶或琥珀酸脱氢酶的遗传改变，嗜酸细胞瘤可能是第三种与氧化静止组织中线粒体ATP产生受损相关的良性肿瘤。此外，复合物I酶活性适度降低，在附近的嗜酸细胞瘤，与正常组织相邻的其他肾脏肿瘤。这表明嗜酸细胞瘤是至少两个系列修饰改变线粒体呼吸链的结果。
Renal oncocytomas are benign tumors characterized by dense accumulation of mitochondria the cause of which remains unknown so far. Consistently, mitochondrial DNA content and the amounts and catalytic activities of several oxidative phosphorylation (OXPHOS) complexes were known to be increased in these tumors, but it was not ascertained that the OXPHOS system was functional. Here we investigated mitochondrial complex I and found that its NADH dehydrogenase activity and protein content were specifically decreased in oncocytomas, in stark contrast with the parallel decrease of all respiratory chain complexes in other, malignant, renal tumors. We conclude that deficiency of complex I in oncocytomas might be the early event causing the increased mitochondrial biogenesis, attempting to compensate for the loss of OXPHOS function. Since other tumors were found to be linked to mitochondrial deficiencies like genetic alterations of fumarate hydratase or succinate dehydrogenase, oncocytoma could be the third type of benign tumor associated with impairment of mitochondrial ATP production in an oxidative, quiescent tissue. Besides, complex I enzyme activity was moderately decreased in the vicinity of oncocytomas, when compared with normal tissue adjacent to other renal tumors. This suggested that oncocytomas are the result of at least two serial modifications altering the mitochondrial respiratory chain.