当前位置: X-MOL 学术Mitochondrion › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Hsp90 and its mitochondrial homologue TRAP-1 independently regulate hypoxia adaptations in Caenorhabditis elegans
Mitochondrion ( IF 3.9 ) Pub Date : 2021-08-05 , DOI: 10.1016/j.mito.2021.08.002
Aakanksha Pant 1 , Keerthi Chittayil Krishnakumar 1 , Navyamol Chakkalaparambil Dileep 1 , Meghana Yamana 1 , Narayanan Meenakshisundaran Alamelu 1 , Khanderao Paithankar 1 , Vijayalakshmi Amash 1 , Sreedhar Amere Subbarao 1
Affiliation  

Mitochondrial adaptations to various environmental cues contribute to cellular and organismal adaptations across multiple model organisms. Due to increased complexity, a direct connection between mitochondrial integrity and oxygen fluctuations, and survival fitness was not demonstrated. Here, using C. elegans as a model system, we studied the role of HIF-1, Hsp90, and TRAP-1 in mitochondrial adaptations during chemical hypoxia. We show that Hsp90mt (Hsp90 mutant) but not HIF-1mt (HIF-1 mutant) affects hypoxia adaptation in nematodes. TRAP-1KD (TRAP-1 knockdown) interfered with the survival and fecundity of worms. Compared to Hsp90mt, TRAP-1KD has induced a significant decrease in mitochondrial integrity and oxygen consumption rate. The complex I inhibitor rotenone did not affect ATP levels in Hsp90mt worms. However, ATP levels were decreased in TRAP-1KD worms under similar conditions. The glucose restriction has reduced, and glucose supplementation has increased the survival rate in Hsp90mt worms. Neither glucose restriction nor glucose supplementation has significantly affected the survival of TRAP-1KD worms in response to hypoxia. However, TRAP-1 inhibition using a nanocarrier drug has dramatically reduced the survival rate in response to hypoxia. Our results suggest that Hsp90 and TRAP-1 independently regulate hypoxia adaptations and metabolic plasticity in C. elegans. Considering the emerging roles of TRAP-1 in altered energy metabolism and cellular adaptations, our findings gain importance.



中文翻译:

Hsp90及其线粒体同源物TRAP-1独立调节秀丽隐杆线虫的缺氧适应

线粒体对各种环境线索的适应有助于跨多种模式生物的细胞和有机体适应。由于复杂性增加,线粒体完整性和氧气波动之间的直接联系以及生存适应性没有得到证实。在这里,我们使用秀丽隐杆线虫作为模型系统,研究了 HIF-1、Hsp90 和 TRAP-1 在化学缺氧期间线粒体适应中的作用。我们显示 Hsp90 mt(Hsp90 突变体)而不是 HIF-1 mt(HIF-1 突变体)影响线虫的缺氧适应。TRAP-1 KD(TRAP-1 敲低)干扰了蠕虫的生存和繁殖力。与 Hsp90 mt相比,TRAP-1 KD导致线粒体完整性和耗氧率显着降低。复合物 I 抑制剂鱼藤酮不影响 Hsp90 mt蠕虫中的 ATP 水平。然而,在类似条件下,TRAP-1 KD蠕虫的 ATP 水平降低。葡萄糖限制减少了,葡萄糖补充提高了 Hsp90 mt蠕虫的存活率。葡萄糖限制和葡萄糖补充都没有显着影响 TRAP-1 KD蠕虫对缺氧的反应。然而,使用纳米载体药物的 TRAP-1 抑制显着降低了对缺氧反应的存活率。我们的结果表明 Hsp90 和 TRAP-1 独立调节缺氧适应和代谢可塑性秀丽隐杆线虫。考虑到 TRAP-1 在改变能量代谢和细胞适应中的新兴作用,我们的研究结果变得越来越重要。

更新日期:2021-08-15
down
wechat
bug