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Title: Mitochondrial fragmentation in excitotoxicity requires ROCK activation
Author: Martorell Riera, Alejandro
Segarra Mondéjar, Marc
Reina del Pozo, Manuel
Martínez Estrada, Ofelia María
Soriano Zaragoza, Francesc X. (Francesc Xavier)
Keywords: Mitocondris
Patologia cel·lular
Cellular pathology
Issue Date: 3-May-2015
Publisher: Landes Bioscience
Abstract: Mitochondria morphology constantly changes through fission and fusion processes that regulate mitochondrial function, and it therefore plays a prominent role in cellular homeostasis. Cell death progression is associated with mitochondrial fission. Fission is mediated by the mainly cytoplasmic Drp1, which is activated by different post-translational modifications and recruited to mitochondria to perform its function. Our research and other studies have shown that in the early moments of excitotoxic insult Drp1 must be nitrosylated to mediate mitochondrial fragmentation in neurons. Nonetheless, mitochondrial fission is a multistep process in which filamentous actin assembly/disassembly and myosin-mediated mitochondrial constriction play prominent roles. Here we establish that in addition to nitric oxide production, excitotoxicity-induced mitochondrial fragmentation also requires activation of the actomyosin regulator ROCK. Although ROCK1 has been shown to phosphorylate and activate Drp1, experiments using phosphor-mutant forms of Drp1 in primary cortical neurons indicate that in excitotoxic conditions, ROCK does not act directly on Drp1 to mediate fission, but may act on the actomyosin complex. Thus, these data indicate that a wider range of signaling pathways than those that target Drp1 are amenable to be inhibited to prevent mitochondrial fragmentation as therapeutic option
Note: Versió postprint del document publicat a:
It is part of: Cell Cycle, 2015, vol. 14, num. 9, p. 1365-1369
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ISSN: 1538-4101
Appears in Collections:Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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