Mislocalization of mitochondria and compromised renal function and oxidative stress resistance in Drosophila SesB mutants.
Mislocalization of mitochondria and compromised renal function and oxidative stress resistance in Drosophila SesB mutants.
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DOI：
10.1152/physiolgenomics.00147.2009
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发表时间：
2010-03
影响因子：
4.6
通讯作者：
Selim Terhzaz;P. Cabrero;Venkateswara R. Chintapalli;S. Davies;J. Dow
中科院分区：
文献类型：
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作者：
Selim Terhzaz;P. Cabrero;Venkateswara R. Chintapalli;S. Davies;J. Dow
线粒体在细胞内代谢活动强烈的部位聚集，但这种位置的适应性价值尚不清楚。在果蝇中，sesB 编码普遍存在的腺嘌呤核苷酸转位酶同工型（ANT，线粒体内膜 ATP/ADP 交换器）；无效等位基因是致命的，而低等位基因则对一系列压力源表现出敏感性。在成人肾小管中，线粒体密集，因此 sesB 含量丰富，低等位基因和 RNA 干扰敲低都会导致线粒体失去其在组织中的高度极化分布并变得圆形。基础细胞质和线粒体钙水平均升高，神经肽钙反应受损，并伴有液体分泌缺陷。 sesB 突变体中剩余的线粒体过度活跃，维持耗尽的细胞 ATP 水平，同时产生比正常水平更高水平的过氧化氢。当仅在肾小管主细胞中敲低 sesB 表达时，整个生物体在氧化应激下的存活率就会降低，这意味着肾小管在应激源的稳态反应中的作用受到限制。因此，ANT 表达缺陷的生理影响是广泛且多样的。
Mitochondria accumulate at sites of intense metabolic activity within cells, but the adaptive value of this placement is not clear. In Drosophila, sesB encodes the ubiquitous isoform of adenine nucleotide translocase (ANT, the mitochondrial inner membrane ATP/ADP exchanger); null alleles are lethal, whereas hypomorphic alleles display sensitivity to a range of stressors. In the adult renal tubule, which is densely packed with mitochondria and hence enriched for sesB, both hypomorphic alleles and RNA interference knockdowns cause the mitochondria to lose their highly polarized distribution in the tissue and to become rounded. Basal cytoplasmic and mitochondrial calcium levels are both increased, and neuropeptide calcium response compromised, with concomitant defects in fluid secretion. The remaining mitochondria in sesB mutants are overactive and maintain depleted cellular ATP levels while generating higher levels of hydrogen peroxide than normal. When sesB expression is knocked down in just tubule principal cells, the survival of the whole organism upon oxidative stress is reduced, implying a limiting role for the tubule in homeostatic response to stressors. The physiological impacts of defective ANT expression are thus widespread and diverse.