Expression of the alternative oxidase influences jun n-terminal kinase signaling and cell migration

Ana Andjelković, Amelia Mordas, Lyon Bruinsma, Annika Ketola, Giuseppe Cannino, Luca Giordano, Praveen K. Dhandapani, Marten Szibor, Eric Dufour, Howard T. Jacobs

    Research output: Contribution to journalArticleScientificpeer-review

    6 Citations (Scopus)

    Abstract

    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 AOXexpressing 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.

    Original languageEnglish
    Article numbere00110-18
    JournalMolecular and Cellular Biology
    Volume38
    Issue number24
    DOIs
    Publication statusPublished - 2018
    MoE publication typeNot Eligible

    Keywords

    • Alternative oxidase
    • AP-1
    • Jun N-terminal kinase
    • Transcription
    • Wound healing

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