Expression of the Alternative Oxidase Influences Jun N-Terminal Kinase Signaling and Cell Migration.
Expression of the Alternative Oxidase Influences Jun N-Terminal Kinase Signaling and Cell Migration.
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DOI：
10.1128/mcb.00110-18
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发表时间：
2018-12-15
影响因子：
5.3
通讯作者：
Jacobs HT
中科院分区：
文献类型：
--
作者：
Andjelković A;Mordas A;Bruinsma L;Ketola A;Cannino G;Giordano L;Dhandapani PK;Szibor M;Dufour E;Jacobs HT
Jun N-末端激酶（JNK）信号转导的下调抑制了不同模型系统中的细胞迁移。在果蝇蛹发育过程中，胸背上皮JNK信号减弱导致中线闭合缺陷，导致裂胸。Jun N-末端激酶（JNK）信号转导的下调抑制了不同模型系统中的细胞迁移。在果蝇蛹发育中，胸背上皮中JNK信号减弱会导致中线闭合缺陷，从而导致胸裂。在这里，我们报告说，伴随表达的玻璃海鞘交替氧化酶（AOX）能够补偿JNK通路下调，基本上纠正了裂胸表型。AOX表达还促进了永生化小鼠胚胎成纤维细胞（iMEFs）的伤口愈合行为和单细胞迁移，抵消了JNK通路抑制的作用。然而，AOX不能拯救由敲低AP-1转录因子（JNK的典型靶点）引起的发育表型，也不能拯救其靶点，并且对AP-1依赖性转录没有影响。在伤口愈合试验中，表达AOX的iMEFs的迁移受到抗霉素A的不同刺激，抗霉素A通过AOX重定向呼吸电子流，改变线粒体ATP和产热之间的平衡。由于影响线粒体ATP的其他治疗方法并不刺激伤口愈合，我们提出增加线粒体产热是AOX在这些不同背景下促进细胞迁移的最可能的主要作用机制。
Downregulation of Jun N-terminal kinase (JNK) signaling inhibits cell migration in diverse model systems. In Drosophila pupal development, attenuated JNK signaling in the thoracic dorsal epithelium leads to defective midline closure, resulting in cleft thorax. Downregulation of Jun N-terminal kinase (JNK) signaling inhibits cell migration in diverse model systems. In Drosophila pupal development, attenuated JNK signaling in the thoracic dorsal epithelium leads to defective midline closure, resulting in cleft thorax. Here we report that concomitant expression of the Ciona intestinalis alternative oxidase (AOX) was able to compensate for JNK pathway downregulation, substantially correcting the cleft thorax phenotype. AOX expression also promoted wound-healing behavior and single-cell migration in immortalized mouse embryonic fibroblasts (iMEFs), counteracting the effect of JNK pathway inhibition. However, AOX was not able to rescue developmental phenotypes resulting from knockdown of the AP-1 transcription factor, the canonical target of JNK, nor its targets and had no effect on AP-1-dependent transcription. The migration of AOX-expressing iMEFs in the wound-healing assay was differentially stimulated by antimycin A, which redirects respiratory electron flow through AOX, altering the balance between mitochondrial ATP and heat production. Since other treatments affecting mitochondrial ATP did not stimulate wound healing, we propose increased mitochondrial heat production as the most likely primary mechanism of action of AOX in promoting cell migration in these various contexts.