Latest Reviews

  • Review Article |

    The mitochondrial proteome comprises ~1,000–1,500 nuclear-encoded and mitochondrial-encoded proteins. To ensure proper mitochondrial function, cells use multiple mechanisms of quality control that survey mitochondrial protein biogenesis, import and folding, and allow mitochondria to adapt to the changing needs as well as to respond to stresses that compromise proteostasis.

    • Jiyao Song
    • , Johannes M. Herrmann
    •  & Thomas Becker
  • Review Article |

    Various physiological processes including development and maintenance of epithelia, cell–cell fusion, neuronal function and immune responses rely on the establishment of direct cell–cell contacts. Despite their diversity, the different cell–cell interfaces can be viewed as specialized compartments that perform their distinct functions through common biophysical properties.

    • Brian Belardi
    • , Sungmin Son
    • , James H. Felce
    • , Michael L. Dustin
    •  & Daniel A. Fletcher
  • Review Article |

    Glycosylation is the most abundant and diverse form of protein post-translational modification. Recent technical developments are enabling the dissection of the glycome in single cells, providing new insights into its regulation and roles in physiology and disease, and new possibilities for controlling glycosylation for therapy.

    • Katrine T. Schjoldager
    • , Yoshiki Narimatsu
    • , Hiren J. Joshi
    •  & Henrik Clausen
  • Review Article |

    Non-homologous DNA end joining (NHEJ) is the main repair pathway of DNA double-strand breaks. Recent studies show that synapsis — the crucial pairing of DNA ends — is performed by several mechanisms, and this insight can now be integrated with updates on the DNA end processing and ligation steps of NHEJ, and with NHEJ-related human diseases.

    • Bailin Zhao
    • , Eli Rothenberg
    • , Dale A. Ramsden
    •  & Michael R. Lieber
  • Review Article |

    The newest CRISPR–Cas genome editing technologies enable precise and simplified formation of crops with increased yield, quality, disease resistance and herbicide resistance, as well as accelerated domestication. Recent breakthroughs in CRISPR–Cas plant biotechnologies improve reagent delivery, gene regulation, multiplexed gene editing and directed evolution.

    • Haocheng Zhu
    • , Chao Li
    •  & Caixia Gao
  • Review Article |

    Cultured pluripotent stem cells (PSCs) acquire genetic changes — gains or losses of entire chromosomal regions, or point mutations, including in cancer-associated genes such as TP53. Recent work provides insights into the mechanisms of mutation and selection, which have implications for the use of human PSCs in regenerative medicine.

    • Jason Halliwell
    • , Ivana Barbaric
    •  & Peter W. Andrews
  • Review Article |

    The intestinal epithelium undergoes rapid turnover and is constantly exposed to hostile luminal contents. Recent insights from single-cell transcriptomics and organoid models have revealed that tissue repair is dependent on cell lineage plasticity and signals originating from different niche components.

    • Joep Beumer
    •  & Hans Clevers
  • Review Article |

    This Review discusses the cell types, critical genes and transcription factors involved in bone development and repair. The dysfunctional cellular and molecular signalling that results in clinical bone disease is also outlined, thus informing the current state of science and clinical practice.

    • Ankit Salhotra
    • , Harsh N. Shah
    • , Benjamin Levi
    •  & Michael T. Longaker
  • Review Article |

    Dispensable, infected or neoplastic cells are removed by programmed cell death, including pathways for apoptosis, necroptosis and pyroptosis. Owing to differences in their mechanisms and physiological outcomes, these cell death pathways have traditionally been viewed as separate entities, but it has become clear that they are mechanistically and functionally connected.

    • Sammy Bedoui
    • , Marco J. Herold
    •  & Andreas Strasser
  • Review Article |

    The nucleolus is a membraneless organelle involved in ribonucleoprotein assembly, including ribosome biogenesis. Recent evidence indicates that the nucleolus is a biomolecular condensate that forms via liquid–liquid phase separation (LLPS), and insights from studies within the LLPS framework are increasing our understanding of the relationship between nucleolar structure and function.

    • Denis L. J. Lafontaine
    • , Joshua A. Riback
    • , Rümeyza Bascetin
    •  & Clifford P. Brangwynne
  • Review Article |

    Histone variants differ from canonical histones in their genomic localization, regulation and function. Incorporation of histone variants endows specific genomic regions with unique features to fine-tune gene expression, contributing to animal development and disease pathogenesis.

    • Sara Martire
    •  & Laura A. Banaszynski
  • Review Article |

    Human organoids are valuable models for the study of development and disease and for drug discovery, thus complementing traditional animal models. The generation of organoids from patient biopsy samples has enabled researchers to study, for example, infectious diseases, genetic disorders and cancers. This Review discusses the advantages, disadvantages and future challenges of the use of organoids as models for human biology.

    • Jihoon Kim
    • , Bon-Kyoung Koo
    •  & Juergen A. Knoblich
  • Review Article |

    Recent studies have highlighted the contribution of RNA to cellular liquid–liquid phase separation and condensate formation. RNA features modulate the composition and biophysical properties of RNA–protein condensates, which have various cellular functions, including RNA transport and localization, supporting catalytic processes and responding to stress.

    • Christine Roden
    •  & Amy S. Gladfelter
  • Review Article |

    Different obstacles can stall the progression of replication forks. Recent studies have revealed that stalled forks are remarkably diverse in their composition and architecture. This plasticity enables fork remodelling, processing and restart in response to specific types of replication stress, thereby influencing tumorigenesis and innate immunity.

    • Matteo Berti
    • , David Cortez
    •  & Massimo Lopes
  • Review Article |

    Extracellular signal-regulated kinase 1 (ERK1) and ERK2 relay cell growth and mitogenic signals to multiple substrates, and thus control essential physiological processes. This Review discusses the regulation of ERKs, and their control of cell proliferation, cell survival, cell growth, cell metabolism, cell migration and cell differentiation.

    • Hugo Lavoie
    • , Jessica Gagnon
    •  & Marc Therrien
  • Review Article |

    The non-canonical addition of non-templated nucleotides to RNA 3′ ends (tailing) by terminal nucleotidyltransferases includes uridylation, mixed-nucleotide tailing and post-transcriptional polyadenylation. Recent studies of human terminal nucleotidyltransferases have revealed their distinct specificities for substrates, including mRNAs, microRNAs and other non-coding RNAs, and how they control RNA stability and activity.

    • Sha Yu
    •  & V. Narry Kim
  • Review Article |

    Extracellular vesicles transfer a variety of cellular components between cells — including proteins, lipids and nucleic acids. There is now evidence indicating that these cargoes, in particular RNAs, can affect the function of recipient cells. Extracellular vesicles are now being actively tested as biomarkers and delivery vehicles for therapeutic agents.

    • Killian O’Brien
    • , Koen Breyne
    • , Stefano Ughetto
    • , Louise C. Laurent
    •  & Xandra O. Breakefield
  • Review Article |

    The unfolded protein response (UPR) comprises a network of signalling pathways that reprogramme transcription, translation and protein modifications to relieve the load of unfolded or misfolded proteins in the endoplasmic reticulum lumen and restore proteostasis. Understanding the regulation of the UPR and the role it has in the pathophysiology of various cell types and organs might open new therapeutic avenues.

    • Claudio Hetz
    • , Kezhong Zhang
    •  & Randal J. Kaufman
  • Review Article |

    The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway senses DNA in the cytoplasm, whether of pathogenic or endogenous (chromatin or mitochondrial) origin, and triggers the interferon response. The mechanisms of DNA recognition and cGAS–STING activation and signalling are now coming into focus, providing insights into the cellular functions of this pathway, including interferon-independent roles.

    • Karl-Peter Hopfner
    •  & Veit Hornung
  • Review Article |

    Autophagy involves engulfment of cellular components into double-membrane vesicles called autophagosomes. The biogenesis of autophagosomes requires the cooperation of multiple proteins and lipids from various membrane sources. Our understanding of the molecular mechanisms of the initiation, growth, bending and closure of autophagosomal membranes is expanding at a rapid pace.

    • Hitoshi Nakatogawa
  • Review Article |

    Circular RNAs, which are produced through back-splicing of exons, are emerging as key regulators of immune responses and cell proliferation. Recent studies have shed new light on the biogenesis and functions of circular RNAs, which include the modulation of transcription and splicing, and interference with microRNAs and other cellular signalling pathways.

    • Ling-Ling Chen
  • Review Article |

    G-quadruplexes (G4s) are structures formed in guanine-rich DNA or RNA, which are linked to transcription, translation, chromatin biology, genome instability and RNA modifications. Recent studies connect G4 formation with cancer-cell lethality and indicate that G4s could be therapeutic targets.

    • Dhaval Varshney
    • , Jochen Spiegel
    • , Katherine Zyner
    • , David Tannahill
    •  & Shankar Balasubramanian
  • Consensus Statement
    | Open Access

    In this Consensus Statement, the authors (on behalf of the EMT International Association) propose guidelines to define epithelial–mesenchymal transition, its phenotypic plasticity and the associated multiple intermediate epithelial–mesenchymal cell states. Clarification of nomenclature and definitions will help reduce misinterpretation of research data generated in different experimental model systems and promote cross-disciplinary collaboration.

    • Jing Yang
    • , Parker Antin
    • , Geert Berx
    • , Cédric Blanpain
    • , Thomas Brabletz
    • , Marianne Bronner
    • , Kyra Campbell
    • , Amparo Cano
    • , Jordi Casanova
    • , Gerhard Christofori
    • , Shoukat Dedhar
    • , Rik Derynck
    • , Heide L. Ford
    • , Jonas Fuxe
    • , Antonio García de Herreros
    • , Gregory J. Goodall
    • , Anna-Katerina Hadjantonakis
    • , Ruby J. Y. Huang
    • , Chaya Kalcheim
    • , Raghu Kalluri
    • , Yibin Kang
    • , Yeesim Khew-Goodall
    • , Herbert Levine
    • , Jinsong Liu
    • , Gregory D. Longmore
    • , Sendurai A. Mani
    • , Joan Massagué
    • , Roberto Mayor
    • , David McClay
    • , Keith E. Mostov
    • , Donald F. Newgreen
    • , M. Angela Nieto
    • , Alain Puisieux
    • , Raymond Runyan
    • , Pierre Savagner
    • , Ben Stanger
    • , Marc P. Stemmler
    • , Yoshiko Takahashi
    • , Masatoshi Takeichi
    • , Eric Theveneau
    • , Jean Paul Thiery
    • , Erik W. Thompson
    • , Robert A. Weinberg
    • , Elizabeth D. Williams
    • , Jianhua Xing
    • , Binhua P. Zhou
    •  & Guojun Sheng
  • Review Article |

    Development and homeostasis are dependent on rapid cell turnover, achieved by the programmed death and subsequent engulfment and breakdown of cells, a process known as efferocytosis. Defects in efferocytosis have been linked to a wide range of diseases; ongoing research therefore aims to better understand efferocytosis processes so as to uncover new therapeutic targets.

    • Emilio Boada-Romero
    • , Jennifer Martinez
    • , Bradlee L. Heckmann
    •  & Douglas R. Green
  • Review Article |

    Telomere length is maintained by telomerase, which comprises a reverse transcriptase and a template RNA. Telomerase activity is disrupted in several genetic disorders, but is commonly increased in cancer. Recent studies have uncovered many regulatory mechanisms of telomerase and how telomerase upregulation in cancer is achieved.

    • Caitlin M. Roake
    •  & Steven E. Artandi
  • Review Article |

    Cells maximize the repertoire of functions produced from their genome through introducing diversity at each stage of the gene expression process, including at the post-translational level. New advances in proteomics and interactomics have begun to shed light on the extent to which diversity is introduced on the proteome level and by the organization of proteins into modular interaction networks.

    • Isabell Bludau
    •  & Ruedi Aebersold
  • Review Article |

    Reactive oxygen species (ROS) were originally associated with cellular damage and disease. However, ROS, notably hydrogen peroxide, at low physiological levels also engage in physiological signalling, supporting cellular responses and adaptation to changing environments and stress. Accordingly, controlling specific ROS-mediated signalling pathways offers new perspectives for a more refined redox medicine.

    • Helmut Sies
    •  & Dean P. Jones
  • Review Article |

    The transcriptional response to hypoxia and the role of hypoxia inducible factors have been extensively studied. Yet, hypoxic cells also adapt to hypoxia by modulating protein synthesis, metabolism and nutrient uptake. Understanding these processes could shed light on pathologies associated with hypoxia, including cardiovascular diseases and cancer, and disease mechanisms, such as inflammation and wound repair.

    • Pearl Lee
    • , Navdeep S. Chandel
    •  & M. Celeste Simon
  • Review Article |

    The mechanical and dynamic properties of microtubules are determined by their complement of subunits, known as tubulin isotypes, and the post-translational modifications found on these isotypes. This concept is known as the ‘tubulin code’. The regulation of microtubules and microtubule-associated proteins by this code is critical for the correct function of a range of tissues. Consequently, recent studies have linked perturbation of the tubulin code to disease, including neurodegenerative diseases.

    • Carsten Janke
    •  & Maria M. Magiera
  • Review Article |

    BRCA1 and its partner BARD1 support repair of double-strand breaks by homologous recombination and protect replication forks from damage. Recent studies have improved our understanding of the molecular mechanisms of these tumour-suppressive functions of BRCA1–BARD1 and how they are subverted in therapy-resistant cancers.

    • Madalena Tarsounas
    •  & Patrick Sung
  • Review Article |

    Mitochondrial networks are dynamically remodelled via fusion, fission and ultrastructural changes to mitochondrial membranes. These mitochondrial membrane dynamics are tightly coupled to cell function, with morphological changes to mitochondria accompanying a multitude of processes as diverse as cell pluripotency, division, differentiation, senescence and death. Accordingly, disturbed dynamics of mitochondrial membranes are linked to severe human disorders.

    • Marta Giacomello
    • , Aswin Pyakurel
    • , Christina Glytsou
    •  & Luca Scorrano
  • Review Article |

    The MYC oncoproteins are transcription factors, but the molecular mechanism of their oncogenic activity is unclear. MYC proteins promote transcription termination in stress conditions, which is proposed to increase cellular resilience to stress and to promote tumorigenesis independently of changes in the expression of their target genes.

    • Apoorva Baluapuri
    • , Elmar Wolf
    •  & Martin Eilers
  • Review Article |

    During cell division, the distribution of membrane-bound organelles needs to be tightly regulated to ensure the proper composition and function of daughter cells. Recent studies have shed light on the range of complex and dynamic mechanisms needed to mediate organelle inheritance and membrane remodelling during cell division.

    • Jeremy G. Carlton
    • , Hannah Jones
    •  & Ulrike S. Eggert
  • Review Article |

    Mammalian genomes generate long non-coding RNAs, which are degraded by the RNA surveillance machinery. This regulated degradation is vital for various processes, including for genome integrity, stem cell pluripotency and immune cell activation. Consequently, defects in RNA surveillance cause human diseases and developmental disorders.

    • Lekha Nair
    • , Hachung Chung
    •  & Uttiya Basu
  • Review Article |

    Ageing is characterized by the functional decline of tissues and organs and increased risk of ageing-associated disorders, and this decline is associated with epigenetic changes. Recently, ‘rejuvenating’ interventions, such as metabolic manipulation, partial cell reprogramming, heterochronic parabiosis and senescent cell ablation, have been proposed to extend healthspan and lifespan by modulating the epigenome.

    • Weiqi Zhang
    • , Jing Qu
    • , Guang-Hui Liu
    •  & Juan Carlos Izpisua Belmonte
  • Perspective |

    R-loops (three-stranded RNA–DNA structures) are often associated with transcription defects, DNA damage and genome instability, but ‘regulatory’ R-loops can promote gene regulation, telomere stability and DNA repair. This dual functionality of R-loops requires tight control of their formation, location and timely removal.

    • Christof Niehrs
    •  & Brian Luke
  • Review Article |

    The mTOR pathway integrates diverse environmental cues to control biomass accumulation and metabolism by modulating key cellular processes, including protein synthesis and autophagy. Dysregulation of mTOR signalling has been implicated in metabolic disorders, neurodegeneration, cancer and ageing, and is thus a promising target for pharmacological intervention.

    • Grace Y. Liu
    •  & David M. Sabatini
  • Review Article |

    Cholesterol is an important structural component of all animal cell membranes that functions in various processes, including membrane dynamics and cell signalling, and is also a precursor of other molecules. Deregulation of cholesterol metabolism — biosynthesis, dietary absorption and cellular uptake, storage and efflux — is linked to many diseases, including cardiovascular and genetic diseases, and cancer. A better understanding of cholesterol metabolism offers the possibility to control systemic cholesterol levels to improve human health.

    • Jie Luo
    • , Hongyuan Yang
    •  & Bao-Liang Song
  • Review Article |

    Animal circadian rhythms are controlled by central and peripheral molecular clocks, whose components generate oscillations in their own abundance and activity. Insights into how these clocks time the function of organs and tissues is increasing our understanding of animal physiology.

    • Alina Patke
    • , Michael W. Young
    •  & Sofia Axelrod
  • Review Article |

    Lysosomes are mainly associated with cellular waste disposal. But it has recently been discovered that by integrating various environmental cues, they have a broader role as regulatory hubs for cellular and organismal homeostasis. The modulation of lysosome function could thus be a promising therapeutic strategy for the treatment of cancer as well as metabolic and neurodegenerative disorders.

    • Andrea Ballabio
    •  & Juan S. Bonifacino
  • Review Article |

    AAA+ proteins are macromolecular machines that remodel a vast array of cellular substrates, including protein aggregates, macromolecular complexes and polymers. Recent advances in cryo-electron microscopy have enabled visualization of them while in action, leading to a better understanding of the mechanisms of engagement and processing of their diverse substrates.

    • Cristina Puchades
    • , Colby R. Sandate
    •  & Gabriel C. Lander
  • Review Article |

    Although organelles compartmentalize eukaryotic cells, they can communicate and integrate their activities by connecting at membrane contact sites (MCSs). The roles of MCSs in biology are becoming increasingly clear, with MCSs now known to function in intracellular signalling, lipid metabolism, membrane dynamics, organelle biogenesis and the cellular stress response.

    • William A. Prinz
    • , Alexandre Toulmay
    •  & Tamas Balla
  • Review Article |

    Endosomal sorting complexes required for transport (ESCRTs) are key membrane remodellers, which drive the budding, scission and sealing of various cellular membranes. Accordingly, ongoing research focuses on how ESCRTs mediate a wide-range of cellular processes, including cytokinesis, endosome maturation, autophagy, membrane repair and viral replication.

    • Marina Vietri
    • , Maja Radulovic
    •  & Harald Stenmark
  • Review Article |

    Novel methods for tracking the progeny of single cells involve prospective lineage tracing, in which DNA barcodes are introduced into single cells and tracked over time, or retrospective lineage tracing, in which somatic mutations are used as DNA barcodes. These methods improve our understanding of cell fates in development, cell differentiation and tissue regeneration.

    • Chloé S. Baron
    •  & Alexander van Oudenaarden
  • Review Article |

    Mitochondria are key executioners of apoptosis. However, it has recently become clear that beyond driving apoptosis, mitochondria also contribute to pro-inflammatory signalling and other types of regulated cell death. These functions are relevant to disease and could be targeted in the treatment of, for example, degenerative disorders, infection and cancer.

    • Florian J. Bock
    •  & Stephen W. G. Tait