{"title":"FMRP gains mitochondrial fission control","authors":"Carissa L. Sirois, Soraya O. Sandoval, Xinyu Zhao","doi":"10.1038/s41556-024-01567-9","DOIUrl":"https://doi.org/10.1038/s41556-024-01567-9","url":null,"abstract":"Mitochondrial fission and fusion are crucial for neurons. The RNA-binding protein FMRP regulates mitochondrial dynamics, including fusion and trafficking in neurons. A study now identifies a mechanism by which FMRP regulates mitochondrial fission.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"98 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adam R. Fenton, Ruchao Peng, Charles Bond, Siewert Hugelier, Melike Lakadamyali, Yi-Wei Chang, Erika L. F. Holzbaur, Thomas A. Jongens
{"title":"FMRP regulates MFF translation to locally direct mitochondrial fission in neurons","authors":"Adam R. Fenton, Ruchao Peng, Charles Bond, Siewert Hugelier, Melike Lakadamyali, Yi-Wei Chang, Erika L. F. Holzbaur, Thomas A. Jongens","doi":"10.1038/s41556-024-01544-2","DOIUrl":"https://doi.org/10.1038/s41556-024-01544-2","url":null,"abstract":"<p>Fragile X messenger ribonucleoprotein (FMRP) is a critical regulator of translation, whose dysfunction causes fragile X syndrome. FMRP dysfunction disrupts mitochondrial health in neurons, but it is unclear how FMRP supports mitochondrial homoeostasis. Here we demonstrate that FMRP granules are recruited to the mitochondrial midzone, where they mark mitochondrial fission sites in axons and dendrites. Endolysosomal vesicles contribute to FMRP granule positioning around mitochondria and facilitate FMRP-associated fission via Rab7 GTP hydrolysis. Cryo-electron tomography and real-time translation imaging reveal that mitochondria-associated FMRP granules are ribosome-rich structures that serve as sites of local protein synthesis. Specifically, FMRP promotes local translation of mitochondrial fission factor (MFF), selectively enabling replicative fission at the mitochondrial midzone. Disrupting FMRP function dysregulates mitochondria-associated MFF translation and perturbs fission dynamics, resulting in increased peripheral fission and an irregular distribution of mitochondrial nucleoids. Thus, FMRP regulates local translation of MFF in neurons, enabling precise control of mitochondrial fission.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"7 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mardi Fink, Kizito Njah, Shyam J. Patel, David P. Cook, Vanessa Man, Francesco Ruso, Arsheen Rajan, Masahiro Narimatsu, Andreea Obersterescu, Melanie J. Pye, Daniel Trcka, Kin Chan, Arshad Ayyaz, Jeffrey L. Wrana
{"title":"Chromatin remodelling in damaged intestinal crypts orchestrates redundant TGFβ and Hippo signalling to drive regeneration","authors":"Mardi Fink, Kizito Njah, Shyam J. Patel, David P. Cook, Vanessa Man, Francesco Ruso, Arsheen Rajan, Masahiro Narimatsu, Andreea Obersterescu, Melanie J. Pye, Daniel Trcka, Kin Chan, Arshad Ayyaz, Jeffrey L. Wrana","doi":"10.1038/s41556-024-01550-4","DOIUrl":"https://doi.org/10.1038/s41556-024-01550-4","url":null,"abstract":"<p>Cell state dynamics underlying successful tissue regeneration are undercharacterized. In the intestine, damage prompts epithelial reprogramming into revival stem cells (revSCs) that reconstitute Lgr5<sup>+</sup> intestinal stem cells (ISCs). Here single-nuclear multi-omics of mouse crypts regenerating from irradiation shows revSC chromatin accessibility overlaps with ISCs and differentiated lineages. While revSC genes themselves are accessible throughout homeostatic epithelia, damage-induced remodelling of chromatin in the crypt converges on Hippo and the transforming growth factor-beta (TGFβ) signalling pathway, which we show is transiently activated and directly induces functional revSCs. Combinatorial gene expression analysis further suggests multiple sources of revSCs, and we demonstrate TGFβ can reprogramme enterocytes, goblet and paneth cells into revSCs and show individual revSCs form organoids. Despite this, loss of TGFβ signalling yields mild regenerative defects, whereas interference in both Hippo and TGFβ leads to profound defects and death. Intestinal regeneration is thus poised for activation by a compensatory system of crypt-localized, transient morphogen cues that support epithelial reprogramming and robust intestinal repair.</p>","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"20 1","pages":""},"PeriodicalIF":21.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"To eat or not to eat","authors":"Stylianos Lefkopoulos","doi":"10.1038/s41556-024-01560-2","DOIUrl":"10.1038/s41556-024-01560-2","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1825-1825"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Seeing tension in cells","authors":"Daryl J. V. David","doi":"10.1038/s41556-024-01562-0","DOIUrl":"10.1038/s41556-024-01562-0","url":null,"abstract":"","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1825-1825"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Navigating human embryogenesis through tailored model selection","authors":"Berna Sozen","doi":"10.1038/s41556-024-01525-5","DOIUrl":"10.1038/s41556-024-01525-5","url":null,"abstract":"Rapid advances in stem cell and bioengineering technologies have sparked a revolution in developmental biology, with stem cell-based embryo models emerging as crucial tools to uncover the intricacies of human embryogenesis. However, making progress relies on precisely posing our questions and selecting our models.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1819-1821"},"PeriodicalIF":17.3,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Lu, Tezin Walji, Benjamin Ravaux, Pratima Pandey, Changsong Yang, Bing Li, Delgermaa Luvsanjav, Kevin H. Lam, Ruihui Zhang, Zhou Luo, Chuanli Zhou, Christa W. Habela, Scott B. Snapper, Rong Li, David J. Goldhamer, David W. Schmidtke, Duojia Pan, Tatyana M. Svitkina, Elizabeth H. Chen
{"title":"Spatiotemporal coordination of actin regulators generates invasive protrusions in cell–cell fusion","authors":"Yue Lu, Tezin Walji, Benjamin Ravaux, Pratima Pandey, Changsong Yang, Bing Li, Delgermaa Luvsanjav, Kevin H. Lam, Ruihui Zhang, Zhou Luo, Chuanli Zhou, Christa W. Habela, Scott B. Snapper, Rong Li, David J. Goldhamer, David W. Schmidtke, Duojia Pan, Tatyana M. Svitkina, Elizabeth H. Chen","doi":"10.1038/s41556-024-01541-5","DOIUrl":"10.1038/s41556-024-01541-5","url":null,"abstract":"Invasive membrane protrusions play a central role in a variety of cellular processes. Unlike filopodia, invasive protrusions are mechanically stiff and propelled by branched actin polymerization. However, how branched actin filaments are organized to create finger-like invasive protrusions is unclear. Here, by examining the mammalian fusogenic synapse, where invasive protrusions are generated to promote cell membrane juxtaposition and fusion, we have uncovered the mechanism underlying invasive protrusion formation. We show that two nucleation-promoting factors for the Arp2/3 complex, WAVE and N-WASP, exhibit different localization patterns in the protrusions. Whereas WAVE is closely associated with the plasma membrane at the leading edge of the protrusive structures, N-WASP is enriched with WIP along the actin bundles in the shafts of the protrusions. During protrusion initiation and growth, the Arp2/3 complex nucleates branched actin filaments to generate low-density actin clouds in which the large GTPase dynamin organizes the new branched actin filaments into bundles, followed by actin-bundle stabilization by WIP, the latter functioning as an actin-bundling protein. Disruption of any of these components results in defective protrusions and failed myoblast fusion in cultured cells and mouse embryos. Together, our study has revealed the intricate spatiotemporal coordination between two nucleation-promoting factors and two actin-bundling proteins in building invasive protrusions at the mammalian fusogenic synapse and has general implications in understanding invasive protrusion formation in cellular processes beyond cell–cell fusion. Lu et al. reveal the spatiotemporal coordination between two nucleation-promoting factors, WAVE and N-WASP, and two actin-bundling proteins, dynamin and WIP, in generating invasive protrusions at the mammalian myoblast fusogenic synapse.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1860-1877"},"PeriodicalIF":17.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Temporal dynamics of membrane contact sites","authors":"Tomas Knedlik, Marta Giacomello","doi":"10.1038/s41556-024-01539-z","DOIUrl":"10.1038/s41556-024-01539-z","url":null,"abstract":"Cell behaviour changes temporally in response to environmental and metabolic cues. This also applies to membrane contact sites (MCSs), where organelles come into close proximity to perform specific functions, such as lipid transfer or calcium signalling. Here, we discuss how MCSs change over time and whether MCSs exhibit circadian rhythmicity.","PeriodicalId":18977,"journal":{"name":"Nature Cell Biology","volume":"26 11","pages":"1822-1824"},"PeriodicalIF":17.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}