{"title":"Molecular machineries shaping the mitochondrial inner membrane","authors":"Oliver Daumke, Martin van der Laan","doi":"10.1038/s41580-025-00854-z","DOIUrl":"https://doi.org/10.1038/s41580-025-00854-z","url":null,"abstract":"<p>Mitochondria display intricately shaped deep invaginations of the mitochondrial inner membrane (MIM) termed cristae. This peculiar membrane architecture is essential for diverse mitochondrial functions, such as oxidative phosphorylation or the biosynthesis of cellular building blocks. Conserved protein nano-machineries such as F<sub>1</sub>F<sub>o</sub>-ATP synthase oligomers and the mitochondrial contact site and cristae organizing system (MICOS) act as adaptable protein–lipid scaffolds controlling MIM biogenesis and its dynamic remodelling. Signal-dependent rearrangements of cristae architecture and MIM fusion events are governed by the dynamin-like GTPase optic atrophy 1 (OPA1). Recent groundbreaking structural insights into these nano-machineries have considerably advanced our understanding of the functional architecture of mitochondria. In this Review, we discuss how the MIM-shaping machineries cooperate to control cristae and crista junction dynamics, including MIM fusion, in response to cellular signalling pathways. We also explore how mutations affecting MIM-shaping machineries compromise mitochondrial functions.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"29 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979572","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":"Histone H1 deamidation regulates DNA double-strand break repair","authors":"Caroline Barranco","doi":"10.1038/s41580-025-00860-1","DOIUrl":"https://doi.org/10.1038/s41580-025-00860-1","url":null,"abstract":"Repair of DNA double-strand breaks requires chromatin opening; however, the mechanisms involved were unclear. This work shows that sequential histone deamidation and acetylation modifications induce chromatin decompaction by reducing positive charge at the DNA–nucleosome interface.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"3 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939956","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":"Fat accumulation in middle-aged male animals","authors":"Kim Baumann","doi":"10.1038/s41580-025-00861-0","DOIUrl":"https://doi.org/10.1038/s41580-025-00861-0","url":null,"abstract":"A distinct population of adipose progenitor cells contributes to the accumulation of visceral white adipose tissue in middle-aged male mice.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"76 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939738","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":"Uncovering the complexity of RNA–protein interactions","authors":"Maïwen Caudron-Herger","doi":"10.1038/s41580-025-00859-8","DOIUrl":"https://doi.org/10.1038/s41580-025-00859-8","url":null,"abstract":"A 2012 study discovered that RNA–binding proteins are more numerous and diverse than previously thought, many having non-canonical RNA-binding domains.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"123 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933506","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":"The diffraction limit of light taken by storm.","authors":"Maria Pia Cosma","doi":"10.1038/s41580-025-00856-x","DOIUrl":"https://doi.org/10.1038/s41580-025-00856-x","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"115 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915010","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}
Rodrigo Aguilar, Michael Rosenberg, Vered Levy, Jeannie T. Lee
{"title":"An evolving landscape of PRC2–RNA interactions in chromatin regulation","authors":"Rodrigo Aguilar, Michael Rosenberg, Vered Levy, Jeannie T. Lee","doi":"10.1038/s41580-025-00850-3","DOIUrl":"https://doi.org/10.1038/s41580-025-00850-3","url":null,"abstract":"<p>A major unsolved problem in epigenetics is how RNA regulates Polycomb repressive complex 2 (PRC2), a complex that trimethylates histone H3 Lys27 (H3K27me3) to form repressive chromatin. Key questions include how PRC2 binds RNA in vivo and what the functional consequences of binding are. In this Perspective, we expound on the viewpoint that RNA is integral to the stepwise regulation of PRC2 activity. Using the long non-coding RNA <i>XIST</i> and X chromosome inactivation as a model, we discuss evidence indicating that RNA is involved in PRC2 recruitment onto chromatin, in induction of its catalytic activity and in its eviction from chromatin. Studies have also implicated RNA in controlling promoter-proximal pausing of RNA polymerase II. The cumulative data argue that the functional consequences of PRC2–RNA interactions crucially depend on RNA conformation. We recognize that alternative hypotheses exist and therefore we attempt to integrate contrary data. Thus, although an RNA-rich landscape is emerging for Polycomb complexes, additional work is required to resolve a broad range of data interpretations.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"46 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893446","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":"Neurons whisper, tissues respond: neurons as orchestrators of stress responses","authors":"Evandro A. De-Souza","doi":"10.1038/s41580-025-00853-0","DOIUrl":"https://doi.org/10.1038/s41580-025-00853-0","url":null,"abstract":"Evandro De-Souza discusses an article by Dillin and Taylor that revealed the importance of neurons in organism-wide stress responses and the role of such cell-nonautonomous stress responses in ageing.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"5 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866512","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":"Rapid evolution to preserve a conserved function","authors":"Mia T. Levine","doi":"10.1038/s41580-025-00848-x","DOIUrl":"https://doi.org/10.1038/s41580-025-00848-x","url":null,"abstract":"A study that helped explain how lack of sequence conservation can go hand in hand with functional conservation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"3 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819158","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}
Yanqing Liu, Brent R. Stockwell, Xuejun Jiang, Wei Gu
{"title":"p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases","authors":"Yanqing Liu, Brent R. Stockwell, Xuejun Jiang, Wei Gu","doi":"10.1038/s41580-025-00842-3","DOIUrl":"https://doi.org/10.1038/s41580-025-00842-3","url":null,"abstract":"<p>Programmed cell death is a mechanism that is crucial for numerous physiological and pathological processes. Whereas p53-mediated apoptosis is a major cell death pathway in cancer, accumulating evidence indicates that p53 also has crucial roles in controlling different non-apoptotic cell death (NACD) pathways, including ferroptosis, necroptosis, pyroptosis, autophagy-dependent cell death, entotic cell death, parthanatos and paraptosis, and may regulate PANoptosis, cuproptosis and disulfidptosis. Notably, the function of p53 in these NACDs substantially contributes to its biological effects, particularly in cancer development and other pathological processes. In this Review, we discuss recent advances in understanding the roles and underlying mechanisms of p53-mediated NACDs, focusing on ferroptosis, necroptosis and pyroptosis. We discuss the complex and distinct physiological settings in which NACDs are regulated by p53, and potential targeting of p53-regulated NACDs for the treatment of cancer and other human diseases. Finally, we highlight several important questions concerning p53-regulated NACDs that warrant further investigation.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"39 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813623","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}
Eikan Mishima, Toshitaka Nakamura, Sebastian Doll, Bettina Proneth, Maria Fedorova, Derek A. Pratt, José Pedro Friedmann Angeli, Scott J. Dixon, Adam Wahida, Marcus Conrad
{"title":"Recommendations for robust and reproducible research on ferroptosis","authors":"Eikan Mishima, Toshitaka Nakamura, Sebastian Doll, Bettina Proneth, Maria Fedorova, Derek A. Pratt, José Pedro Friedmann Angeli, Scott J. Dixon, Adam Wahida, Marcus Conrad","doi":"10.1038/s41580-025-00843-2","DOIUrl":"https://doi.org/10.1038/s41580-025-00843-2","url":null,"abstract":"<p>Ferroptosis is a necrotic, non-apoptotic cell death modality triggered by unrestrained iron-dependent lipid peroxidation. By unveiling the regulatory mechanisms of ferroptosis and its relevance to various diseases, research over the past decade has positioned ferroptosis as a promising therapeutic target. The rapid growth of this research field presents challenges, associated with potentially inadequate experimental approaches that may lead to misinterpretations in the assessment of ferroptosis. Typical examples include assessing whether an observed phenotype is indeed linked to ferroptosis, and selecting appropriate animal models and small-molecule modulators of ferroptotic cell death. This Expert Recommendation outlines state-of-the-art methods and tools to reliably study ferroptosis and increase the reproducibility and robustness of experimental results. We present highly validated compounds and animal models, and discuss their advantages and limitations. Furthermore, we provide an overview of the regulatory mechanisms and the best-studied players in ferroptosis regulation, such as GPX4, FSP1, SLC7A11 and ACSL4, discussing frequent pitfalls in experimental design and relevant guidance. These recommendations are intended for researchers at all levels, including those entering the expanding and exciting field of ferroptosis research.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"33 1","pages":""},"PeriodicalIF":112.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813625","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}