Nuclear envelope budding is a response to cellular stress

Panagaki, Dimitra; Croft, Jacob T.; Keuenhof, Katharina; Berglund, Lisa Larsson; Andersson, Stefanie; Kohler, Verena; Büttner, Sabrina; Tamás, Markus J.; Nyström, Thomas; Neutze, Richard; Höög, Johanna L.

doi:10.1073/pnas.2020997118

Cited by 30 publications

(43 citation statements)

References 109 publications

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“…Lastly, the removal of INM contents through the proposed mechanism evokes comparisons to the nuclear-to-cytosolic translocation of so-called “mega” RNPs in some Drosophila neurons that proceeds through a vesicular intermediate in the NE lumen ( Speese et al, 2012 ). Similar structures have been observed in yeast upon inhibiting nuclear export ( Ding et al, 2017 Preprint ) and as part of a stress response ( Panagaki et al, 2021 ). Thus, we anticipate that the removal of intranuclear contents through the NE lumen will prove to be a generalizable principle of protein, and perhaps RNA, quality control that will be relevant beyond the yeast system and that has, in fact, already been hypothesized ( Rose and Schlieker, 2012 ).…”

Section: Discussionsupporting

confidence: 67%

Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome

Chandra

Mannino

Thaller

et al. 2021

Journal of Cell Biology

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Mechanisms that turn over components of the nucleus and inner nuclear membrane (INM) remain to be fully defined. We explore how components of the INM are selected by a cytosolic autophagy apparatus through a transmembrane nuclear envelope–localized cargo adaptor, Atg39. A split-GFP reporter showed that Atg39 localizes to the outer nuclear membrane (ONM) and thus targets the INM across the nuclear envelope lumen. Consistent with this, sequence elements that confer both nuclear envelope localization and a membrane remodeling activity are mapped to the Atg39 lumenal domain; these lumenal motifs are required for the autophagy-mediated degradation of integral INM proteins. Interestingly, correlative light and electron microscopy shows that the overexpression of Atg39 leads to the expansion of the ONM and the enclosure of a network of INM-derived vesicles in the nuclear envelope lumen. Thus, we propose an outside–in model of nucleophagy where INM is delivered into vesicles in the nuclear envelope lumen, which can be targeted by the autophagosome.

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Section: Discussionsupporting

confidence: 67%

Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome

Chandra

Mannino

Thaller

et al. 2021

Journal of Cell Biology

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“…1 B, see 5 and 45 min). Electron-dense content, which has also been shown to be protein aggregates in the case of the nucleus ( Panagaki et al, 2021 ), was observed in both the nucleus and mitochondria ( Fig. 1 B, see 15, 30, 45 and 90 min).…”

Section: Resultsmentioning

confidence: 55%

Large organellar changes occur during mild heat shock in yeast

Keuenhof

Berglund

Hill

et al. 2021

Journal of Cell Science

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When the temperature is increased, the heat shock response is activated to protect the cellular environment. The transcriptomics and proteomics of this process are intensively studied, while information about how the cell responds structurally to heat stress is mostly lacking. Here, Saccharomyces cerevisiae were subjected to a mild continuous heat shock (38°C) and intermittently cryo-immobilized for electron microscopy. Through measuring changes in all distinguishable organelle numbers, sizes, and morphologies in over 2100 electron micrographs a major restructuring of the cell's internal architecture during the progressive heat shock was revealed. The cell grew larger but most organelles within it expanded even more, shrinking the volume of the cytoplasm. Organelles responded to heat shock at different times, both in terms of size and number, and adaptations of certain organelles’ morphology (such as the vacuole), were observed. Multivesicular bodies grew to almost 170% in size, indicating a previously unknown involvement in the heat shock response. A previously undescribed electron translucent structure accumulated close to the plasma membrane. This all-encompassing approach provides a detailed chronological progression of organelle adaptation throughout the cellular heat-stress response.

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“…In order to facilitate the transport of macromolecules such as proteins and RNAs between the cytoplasm and the nucleus, the nuclear membrane maintains some pores that allow the passage of hydrophilic molecules smaller than 39 nm ( Panagaki et al, 2021 ). Theoretically, nanodrugs with dimensions smaller than 39 nm and hydrophilicity have the potential for passive nuclear targeting ( Fu et al, 2020 ).…”

Section: Passive Nucleus-targeting Nanodrugsmentioning

confidence: 99%

Nucleus-Targeting Phototherapy Nanodrugs for High-Effective Anti-Cancer Treatment

et al. 2022

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DNA is always one of the most important targets for cancer therapy due to its leading role in the proliferation of cancer cells. Phototherapy kills cancer cells by generating reactive oxygen species (ROS) and local hyperthermia under light. It has attracted extensive interest in the clinical treatment of tumors because of many advantages such as non-invasiveness, high patient compliance, and low toxicity and side effects. However, the short ROS diffusion distance and limited thermal diffusion rate make it difficult for phototherapy to damage DNA deep in the nucleus. Therefore, nucleus-targeting phototherapy that can destroy DNAs via in-situ generation of ROS and high temperature can be a very effective strategy to address this bottleneck. Recently, some emerging nucleus-targeting phototherapy nanodrugs have demonstrated extremely effective anticancer effects. However, reviews in the field are still rarely reported. Here, we comprehensively summarized recent advances in nucleus-targeting phototherapy in recent years. We classified nucleus-targeting phototherapy into three categories based on the characteristics of these nucleus-targeting strategies. The first category is the passive targeting strategy, which mainly targets the nucleus by adjusting the physicochemical characteristics of phototherapy nanomedicines. The second category is to mediate the phototherapy nanodrugs into the nucleus by modifying functional groups that actively target the nucleus. The third category is to assist nanodrugs enter into the nucleus in a light-controlled way. Finally, we provided our insights and prospects for nucleus-targeting phototherapy nanodrugs. This minireview provides unique insights and valuable clues in the design of phototherapy nanodrugs and other nucleus-targeting drugs.

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Nuclear envelope budding is a response to cellular stress

Cited by 30 publications

References 109 publications

Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome

Atg39 selectively captures inner nuclear membrane into lumenal vesicles for delivery to the autophagosome

Large organellar changes occur during mild heat shock in yeast

Nucleus-Targeting Phototherapy Nanodrugs for High-Effective Anti-Cancer Treatment

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