Articles in 2022

The proteins apoptosis regulator BAX (BAX), BCL-2 homologous antagonist/killer (BAK) and BCL-2-related ovarian killer protein (BOK), gasdermins and mixed lineage kinase domain-like protein (MLKL) are key executioners of regulated cell death by forming pores across the plasma or mitochondrial membrane. This Review discusses structural rearrangements during activation and oligomerization of these proteins and highlights commonalities and differences of pore formation mechanisms.

Zhang et al. report that angiogenesis in the chick embryo is supported by migrasomes — recently described organelles produced by migrating cells.

Cockburn et al. report that cells exiting the epidermal stem cell layer show a gradual progression of transcriptional changes during differentiation and retain the ability to divide once differentiation-committed.

The oncoprotein MYC undergoes multimerization to limit transcription–replication conflicts, thereby reducing the formation of DNA double-strand breaks in cancer cells.

Membraneless organelles (MLOs) contribute to intracellular compartmentalization and to various cellular processes. This Review provides a guide to MLOs involved in gene regulation in eukaryotes, discussing their assembly, structure, roles in transcription, RNA processing and translation — particularly in stress conditions — and their disease relevance.

In this World View, Felicity Davis discusses how efforts surrounding diversity, equity and inclusion (DEI) often serve to tick a mandatory box, rather than delivering a meaningful change in the DEI space.

Bera et al. demonstrate that increased viscosity of the surrounding fluid promotes cell migration, supporting tumour cell dissemination and tissue colonization in vivo.

Marina Chekulaeva describes the experiments that showed that microRNAs cause degradation of their target mRNAs.

The genome contains various non-coding regulatory elements, including silencers of gene expression. Recent progress in the identification and characterization of silencers has considerably deepened our understanding of their function, and has shed light on the potential relevance of targeting silencers in therapy for hereditary diseases.

Malka et al. uncover thousands of 5′ uncapped and polyadenylated transcripts (5′ UPTs) and describe their biogenesis through the alternative polyadenylation pathway. 5′ UPTs contribute to the proteome as non-canonical peptides with likely diverse biological functions.

Reyes et al. show that fibroblasts with properties of cellular senescence are present in healthy epithelial tissues and — by upregulating the senescence associated secretory phenotype (SASP) — they support stem-cell function and tissue repair.

Giovanni D’Angelo and Gioele La Manno present the concept of lipotypes, and suggest that lipid composition is an important regulator of cell fate.

AMP-activated protein kinase (AMPK) is a cellular energy sensor canonically activated by increases in AMP/ADP to ATP ratios. Recent advances revealed several non-canonical pathways for AMPK activation, including roles of calcium, nutrients and metabolites, as well as DNA and lysosome damage, providing novel insights into the pathology of AMPK in cancer, metabolic disease, fibrosis and inflammation.

Selective autophagy engages several cargo receptors that target specific, potentially toxic, content (damaged organelles, protein aggregates, pathogens) for lysosomal degradation. Understanding of the mechanisms governing this process in mammals has expanded in recent years, opening the prospects for enhancing selective autophagy to boost cellular quality control capabilities.

Recent studies have expanded our understanding of the mechanisms and functions of ubiquitylation. Pathogens rewrite ubiquitylation to promote infection through unconventional ubiquitylation involving lipids and sugars, and structural studies have revealed that ubiquitin functions involve elaborate multivalent interactions that regulate transcription or protein degradation.

Natascha Drude wanted to combine her academic work in drug development with clinical research. Here’s how she managed to bridge the divide.

This Comment draws attention to cellular protrusions as a source of extracellular vesicles (EVs). These protrusion-derived vesicles expand the repertoire of EVs, impacting current nomenclature and our understanding of EV functions in inter-cellular communication.

Liming Sun brings to attention paper by Li et al. (2012) reporting that necroptosis kinases, RIPK1 and RIPK3, form functional amyloids that regulate cell death signalling.

Zheng et al. show that calcium transients at the endoplasmic reticulum surface trigger condensation of FIP200 and the formation of ULK1 assemblies for autophagosome biogenesis.