Reviews & Analysis

Mitochondrial permeability transition — mediated by the opening of the so-called mitochondrial permeability transition pore — causes abrupt flux of low molecular weight solutes across the generally impermeable inner mitochondrial membrane. Recent studies provide new insights into the molecular nature and mechanisms of the mitochondrial permeability transition pore and the physiological consequences of its opening.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other coronaviruses rely on a cohort of specialized viral proteins to transcribe and replicate their RNA genomes. Recent studies have improved our understanding of coronavirus RNA translation, replication and transcription, and offer new therapeutic targets.

Double-stranded RNAs (dsRNAs) are recognized by designated cellular sensors to mount an immune response. Although dsRNAs are generally of viral origin, dysregulation of several cellular processes can lead to accumulation of endogenous dsRNAs. These self-derived dsRNAs are often associated with immune disorders, but their immunogenicity can also be exploited for immunotherapy.

Cells in the embryo are subject to autonomous and external mechanical forces that help steer embryonic tissue patterning. Technical developments, such as in vitro models of early embryos, allow probing of the roles of mechanical forces in animal and human embryonic development.

Small RNAs (microRNAs, siRNAs, piRNAs and others) function as agents of intercellular communication, particularly in development, reproduction, immunity and inheritance. Chen and Rechavi discuss mechanisms and roles of plant and animal small RNAs in the exchange of information between cells, organisms and even species.

Satellite cells are skeletal muscle stem cells that are largely quiescent. They are activated upon muscle damage and differentiate into muscle cells or return to quiescence. These processes are controlled by cell-intrinsic mechanisms and by signals from the niche, and are deregulated in ageing, leading to impaired muscle regeneration.

Mitochondrial respiration relies on five enzymatic complexes that couple electron transport with proton pumping, leading to ATP synthesis. Recent studies have shed new light on the organization, assembly and mechanisms of the respiratory complexes, including the formation of their larger assemblies — respiratory supercomplexes — and their roles in physiology.

Entry of SARS-CoV-2 into host cells is mediated by the interaction between the viral spike protein and its receptor angiotensin-converting enzyme 2, followed by virus–cell membrane fusion. Worldwide research efforts have provided a detailed understanding of this process at the structural and cellular levels, enabling successful vaccine development for a rapid response to the COVID-19 pandemic.

Recent studies have revolutionized our understanding of the interplay between mRNA poly(A) tails and the processes of translation and mRNA decay in the cytoplasm. Poly(A) tails interact with dedicated RNA-binding proteins and deadenylases, which together determine the impact of poly(A) tails on gene expression.

Integral membrane proteins make up around one quarter of the human proteome and are highly diverse in topology, biophysical features, structure and function. Their biogenesis involves multiple pathways for membrane targeting, insertion into the lipid bilayer, folding and assembly with other subunits. Recent biochemical and structural analyses have provided new insights into these mechanisms.

DNA polymerase theta (Polθ)-mediated end joining is a recently characterized DNA repair pathway that functions in various cellular contexts to repair DNA double-strand breaks that are not repaired by other pathways. Polθ-mediated end joining both helps maintain the genome and causes genome instability, and is an emerging therapeutic target in cancer.

Dietary restriction in rodents and non-human primates affects key nutrient-sensing signalling pathways to increase healthspan and lifespan. This Review discusses these geroprotective mechanisms and recent insights suggesting that dietary restriction results in similar molecular and metabolic changes in humans, contributing to the prevention of ageing-associated diseases.

Machine learning is becoming a widely used tool for the analysis of biological data. However, for experimentalists, proper use of machine learning methods can be challenging. This Review provides an overview of machine learning techniques and provides guidance on their applications in biology.

This Review discusses our current understanding of cell cycle regulation, the functions of cell cycle checkpoints and how disruption of these finely tuned mechanisms is associated with cancer. Insights into these regulatory mechanisms are creating new opportunities for the treatment of cancer.

Deficiency in the protein kinase ATM — a master regulator of double-strand DNA breaks and stress responses — causes ataxia telangiectasia (A-T). Recent studies link A-T with other neurodegenerative disorders, and implicate reactive oxygen species, mitochondrial dysfunction, defects in proteostasis and metabolism, and increased poly(ADP-ribosyl)ation in the aetiology of A-T.

In cells, microtubules are dynamically assembled and disassembled at their growing (plus) tips. Recent insights into microtubule plus tip organization now pave the way for understanding the regulation of microtubule dynamics and for addressing how these dynamics allow microtubules to fulfil their vast repertoire of cellular functions.

Polycomb repressive complex 1 (PRC1) and PRC2 are important gene regulators in various physiological contexts, especially in development. Recent studies have uncovered the molecular mechanisms that enable mammalian PRC1 and PRC2 to identify their genomic target sites, modify chromatin properties and control transcription.

An emerging model of gene regulation posits that DNA, RNA and proteins form condensate nuclear compartments that facilitate cooperative interactions. This Review discusses how compartmentalization can lead to non-stoichiometric molecular interactions and behaviours in transcription, co-transcriptional and post-transcriptional RNA processing, and higher-order chromatin regulation.

Following their biogenesis, autophagosomes undergo maturation into degradative autolysosomes by fusing with late endosomes/lysosomes. This process — involving an array of molecular regulators of membrane dynamics — is essential for autophagic degradation, and its deregulation can lead to disease, including neurodegeneration, muscle diseases and cancer, and propagation of pathogens.

Insulin resistance is one of the earliest manifestations of several human diseases, including type 2 diabetes and cardiovascular disease. This Review discusses the causes of insulin resistance and recent insights into the underlying mechanisms, providing directions for the development of novel therapeutic strategies