Localized translation near the mitochondrial outer membrane: An update

Lesnik, Chen; Golani-Armon, Adi; Arava, Yoav

doi:10.1080/15476286.2015.1058686

Cited by 116 publications

(110 citation statements)

References 96 publications

(136 reference statements)

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“…Potential candidates include the mitochondrial heat shock protein 90 (Hsp90), which is not only a known chaperone of NIK [38], but was also found to deliver proteins to mitochondrial import receptors [39, 40]. Alternatively, mitochondrial localization of NIK may involve localized, co-translational mitochondrial import [41], which could potentially facilitate its protection from being immediately ubiquitinated and degraded. Localization of NIK to mitochondria, its presence in a complex with Drp1, and its regulatory role in Drp1 phosphorylation and mitochondrial localization suggest that NIK functions as a novel fission “sensor.” Thus, it will be interesting to determine whether the association of NIK with mitochondria is dynamic, and possibly induced by specific signals known to promote fission [26, 42–44].…”

Section: Discussionmentioning

confidence: 99%

NIK/MAP3K14 Regulates Mitochondrial Dynamics and Trafficking to Promote Cell Invasion

et al. 2016

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SUMMARY Although the role of NF-κB-inducing kinase (NIK) in immunity is well established, its relevance in cancer is just emerging. Here we describe novel functions for NIK in regulating mitochondrial dynamics and motility to promote cell invasion. We show that NIK is localized to mitochondria in cancer cell lines, ex vivo tumor tissue, and mouse embryonic fibroblasts (MEFs). NIK promotes mitochondrial fission, velocity, and directional migration, resulting in subcellular distribution of mitochondria to the periphery of migrating cells. Moreover, NIK is required for recruitment of Drp1 to mitochondria, forms a complex with Drp1, and regulates Drp1 phosphorylation at Ser-616 and dephosphorylation at Ser-637. Consistent with a role for NIK in regulating mitochondrial dynamics, we demonstrate that Drp1 is required for NIK-dependent, cytokine-induced invasion. Importantly, using MEFs, we demonstrate that the established downstream mediators of NIK signaling, IκB kinase α/β (IKKα/β) and NF-κB, are not required for NIK to regulate cell invasion, Drp1 mitochondrial localization, or mitochondrial fission. Our results establish a new paradigm for IKK-independent NIK signaling and significantly expand the current dogma that NIK is predominantly cytosolic and exclusively regulates NF-κB activity. Overall, these findings highlight the importance of NIK in tumor pathogenesis and invite new therapeutic strategies that attenuate mitochondrial dysfunction through inhibition of NIK and Drp1.

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Section: Discussionmentioning

confidence: 99%

NIK/MAP3K14 Regulates Mitochondrial Dynamics and Trafficking to Promote Cell Invasion

et al. 2016

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“…Third, when examined in other highly polarized cell types, such as neurons, other studies have also shown extremely high rates of RNA subcellular localization (Bruckenstein et al 1990;Olink-Coux and Hollenbeck 1996;Mercer et al 2008). Finally, recent studies have shown that mRNAs encoding common organelle-specific gene products, such as those that function in the ER, mitochondria, and P bodies, can also be copurified bound to these organelles (Decker and Parker 2012;Reid and Nicchitta 2012;Kraut-Cohen et al 2013;Lesnik et al 2015). Indeed, these biochemical approaches have suggested that as much as 50% of cytosolic protein-encoding transcripts are translated on ER (Reid and Nicchitta 2012;Jagannathan et al 2014).…”

Section: Subcellular Localization Prevalencementioning

confidence: 99%

Diverse and pervasive subcellular distributions for both coding and long noncoding RNAs

et al. 2016

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In a previous analysis of 2300 mRNAs via whole-mount fluorescent in situ hybridization in cellularizing Drosophila embryos, we found that 70% of the transcripts exhibited some form of subcellular localization. To see whether this prevalence is unique to early Drosophila embryos, we examined ∼8000 transcripts over the full course of embryogenesis and ∼800 transcripts in late third instar larval tissues. The numbers and varieties of new subcellular localization patterns are both striking and revealing. In the much larger cells of the third instar larva, virtually all transcripts observed showed subcellular localization in at least one tissue. We also examined the prevalence and variety of localization mechanisms for >100 long noncoding RNAs. All of these were also found to be expressed and subcellularly localized. Thus, subcellular RNA localization appears to be the norm rather than the exception for both coding and noncoding RNAs. These results, which have been annotated and made available on a recompiled database, provide a rich and unique resource for functional gene analyses, some examples of which are provided.

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“…This process, mediated by displacement of translational repressors, links dynamic regulation of mitochondrial quality control and oxidative phosphorylation (OXPHOS) (43, 44). Parkin-dependent mitophagy has also been implicated in metabolic programming, e.g.…”

Section: Mitochondrial Structural Remodeling: Rearranging and Recmentioning

confidence: 99%