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This Review provides an overview of modern mechanistic theories and critically examines two main groups of ageing theories—error and program based—in the context of ageing patterns, genetic manipulations and longevity drugs.
This Review discusses emerging insights into SEL1L–HRD1-mediated endoplasmic reticulum-associated degradation, including the underlying molecular mechanisms, physiological relevance for human disease and potential therapeutic opportunities.
This Review discusses the mechanisms underlying the insertion of α-helical proteins into the mitochondrial outer membrane and highlights the role of convergent evolution in the process by comparing key biogenesis factors across several species.
This Review discusses the diversity of human fibroblasts, including their embryonic origin and precursor populations, and highlights their crucial role in orchestrating organ function and modulating immune responses in healthy and disease contexts.
This Review discusses the role of phosphatidylinositol phosphates and their modifying enzymes in modulating cell motility and adhesion and emphasizes the potential of targeting the associated pathways for therapeutic benefit.
Auwerx and colleagues review recent advances in mitochondrial genetics, proteomics and biochemistry that emphasize the far-reaching impact of mitochondrial genetic variation and the role of mitochondria as finely tuned signalling hubs.
This Review discusses the recent advances in experimental approaches to interrogate the mechanical forces that mediate tissue deformations during development, highlighting the insights afforded at both the cellular and tissue scales.
Cells respond to mitochondrial protein import stress by regenerating clogged import sites and inducing stress responses. Mitochondria are thus tightly integrated into the cellular proteostasis and stress-response network to maintain cell viability.
Recent developments in single-cell technologies have increased our understanding of how the coordinated activities of transcription factors in different quiescent cells and differentiated cells maintain reversible cell cycle arrest.
Narendra and Youle review the current understanding of the role of PINK1–Parkin in the quality control of mitophagy, highlighting the underlying mechanisms and physiological relevance of the pathway, as well as its role in neuroprotection.
Man and Kanneganti discuss how pattern-recognition sensors in innate immune cells recognize and respond to cell-death signatures, and highlight molecular targets for potential therapeutic development.
Gasdermins are a family of proteins that form membrane pores and elicit pyroptosis. This Review discusses recent work highlighting their regulation and emerging biological roles, including in non-lethal pore formation and host defence.
The subcellular localization of numerous mRNAs has been demonstrated. This Review presents the different means of mRNA localization described and discusses how they can account for the widespread occurrence of this phenomenon.
R-loops and G-quadruplexes are non-canonical nucleic acid structures with known roles in genome organization. Here, Wulfridge and Sarma highlight emerging roles in DNA repair and transcriptional and epigenetic gene regulation.
Several processes of regulated cell death engage or use mitochondria, which are thus central hubs that not only coordinate cell death but also elicit non-lethal signalling mediated by mitochondrial outer membrane permeabilization.
Ferroptosis is a form of cell death that is characterized by morphological abnormalities of mitochondria and the overwhelming peroxidation of phospholipids. Certain tumours are susceptible to ferroptosis, which could be exploited to treat cancers.
Granath-Panelo and Kajimura review emerging evidence of mitochondrial heterogeneity in different contexts and discuss how mitochondrial malleability contributes to cell fate determination and tissue remodelling.
Metastatic colonization involves cancer-cell-intrinsic mechanisms and microenvironmental interactions, and a better understanding of the factors that influence the final, post-extravasation phases is crucial for therapeutically targeting metatstasis.
Mathiowetz and Olzmann review our current understanding of the mechanisms of lipid droplet biogenesis and turnover, the transfer of lipids and metabolites at membrane contact sites, and the role of lipid droplets in regulating fatty acid flux in lipotoxicity and cell death.
In this Review, Dai, Stockwell, Kroemer, Tang and colleagues offer a comprehensive discussion of the molecular regulation of ferroptosis and highlight how this may be potentially leveraged for therapeutic benefit for disease treatment.
