Nuclear envelope budding and its cellular functions

The nuclear pore complex (NPC) has long been assumed to be the sole route across the nuclear envelope, and under normal homeostatic conditions it is indeed the main mechanism of nucleo-cytoplasmic transport. However, it has also been known that e.g. herpesviruses cross the nuclear envelope utilizing a pathway entitled nuclear egress or envelopment/de-envelopment. Despite this, a thread of observations suggests that mechanisms similar to viral egress may be transiently used also in healthy cells. It has since been proposed that mechanisms like nuclear envelope budding (NEB) can facilitate the transport of RNA granules, aggregated proteins, inner nuclear membrane proteins, and mis-assembled NPCs. Herein, we will summarize the known roles of NEB as a physiological and intrinsic cellular feature and highlight the many unanswered questions surrounding these intriguing nuclear events

Nuclear envelope budding is a response to cellular stress

Nuclear envelope budding (NEB) is a recently discovered alternative pathway for nucleocytoplasmic communication distinct from the movement of material through the nuclear pore complex. Through quantitative electron microscopy and tomography, we demonstrate how NEB is evolutionarily conserved from early protists to human cells. In the yeast Saccharomyces cerevisiae, NEB events occur with higher frequency during heat shock, upon exposure to arsenite or hydrogen peroxide, and when the proteasome is inhibited. Yeast cells treated with azetidine-2-carboxylic acid, a proline analog that induces protein misfolding, display the most dramatic increase in NEB, suggesting a causal link to protein quality control. This link was further supported by both localization of ubiquitin and Hsp104 to protein aggregates and NEB events, and the evolution of these structures during heat shock. We hypothesize that NEB is part of normal cellular physiology in a vast range of species and that in S. cerevisiae NEB comprises a stress response aiding the transport of protein aggregates across the nuclear envelope

Frequencies of micronucleated binucleated cells (BNMN) and micronuclei (MN) as well as cytokinesis block proliferation index (CBPI) values in cultured human lymphocytes which have been treated with Chios mastic oil (CMO), mitomycin-C (MMC) (0.05 <i>μ</i>g/ml) and their mixture.

<p>BN: binucleated cells; BNMN: micronucleated binucleated cells; MN: micronuclei; CBPI: Cytokinesis Block Proliferation Index; CMO: Chios Mastic Oil; MMC: Mitomycin-C; MF (‰)±se, mean frequencies (‰)±standard error; MN were scored in 2000 binucleated lymphocytes per experimental point;</p><p>¹ Significant difference compared to control at p<0.001;</p><p>^a Significant difference compared to MMC at p<0.001; G-test for BNMN and MN; <i>χ</i>^<i>2</i> for CBPI</p><p>Frequencies of micronucleated binucleated cells (BNMN) and micronuclei (MN) as well as cytokinesis block proliferation index (CBPI) values in cultured human lymphocytes which have been treated with Chios mastic oil (CMO), mitomycin-C (MMC) (0.05 <i>μ</i>g/ml) and their mixture.</p

Frequencies of small, large, twin and total mosaic spots in <i>D</i>.<i>melanogaster</i> wings of individuals treated with Chios mastic oil (CMO), mitomycin-C (MMC) (2.5 <i>μ</i>g/ml) or their mixture.

<p>¹The number of mutant spots is given in parenthesis. Symbols next to values signify the following: +, positive mutagenic effect;-, no mutagenic effect; i, inconclusive effect (p = 0.05); Statistical diagnosis according to Frei & Würgler [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0130498#pone.0130498.ref038" target="_blank">38</a>].</p><p>Frequencies of small, large, twin and total mosaic spots in <i>D</i>.<i>melanogaster</i> wings of individuals treated with Chios mastic oil (CMO), mitomycin-C (MMC) (2.5 <i>μ</i>g/ml) or their mixture.</p

Genotoxic and Antigenotoxic Assessment of Chios Mastic Oil by the In Vitro Micronucleus Test on Human Lymphocytes and the In Vivo Wing Somatic Test on Drosophila

International audienceChios mastic oil (CMO), the essential oil derived from Pistacia lentiscus (L.) var. chia (Duham), has generated considerable interest because of its antimicrobial, anticancer, antioxidant and other beneficial properties. In the present study, the potential genotoxic activity of CMO as well as its antigenotoxic properties against the mutagenic agent mitomycin-C (MMC) were evaluated by employing the in vitro Cytokinesis Block MicroNucleus (CBMN) assay and the in vivo Somatic Mutation And Recombination Test (SMART). In the in vitro experiments, lymphocytes were treated with 0.01, 0.05 and 0.10% (v/v) of CMO with or without 0.05 μg/ml MMC, while in the in vivo assay Drosophila larvae were fed with 0.05, 0.10, 0.50 and 1.00% (v/v) of CMO with or without 2.50 μg/ml MMC. CMO did not significantly increase the frequency of micronuclei (MN) or total wing spots, indicating lack of mutagenic or recombinogenic activity. However, the in vitro analysis suggested cytotoxic activity of CMO. The simultaneous administration of MMC with CMO did not alter considerably the frequencies of MMC-induced MN and wing spots showing that CMO doesn't exert antigenotoxic or antirecombinogenic action. Therefore, CMO could be considered as a safe product in terms of genotoxic potential. Even though it could not afford any protection against DNA damage, at least under our experimental conditions, its cytotoxic potential could be of interest