Exogenous treatment with the nicotinamide adenine dinucleotide (NAD⁺) precursor nicotinamide mononucleotide (NMN) is presumed to elevate NAD⁺ levels through its direct incorporation via the canonical NAD⁺ recycling pathway. Here, metabolic tracing of strategically designed NMN isotopologues in vivo reveals that the gut microbiome mediates NMN deamidation and uptake into the NAD⁺ metabolome via the de novo pathway.

The toolbox to manipulate gene function in human pluripotent stem cell models is large and growing: we review the state-of-the-art methods to perform robust loss-, gain-, and change-of-function studies, including emerging approaches that combine single-cell genomics to expand the scope of such investigations.

Lipid droplets (LDs) make physical contacts with various organelles in eukaryotic cells including mitochondria. The existence of these contacts is well-known but poorly described. Here, we review recent advances in the understanding of the physical and functional links between LDs and mitochondria, and their implications in fatty acid transfer, cell signaling, and various diseases.

Aging is associated with an impairment in stem cell function and several strategies for stem cell rejuvenation have been proposed: exercise, dietary restriction, reprogramming, senolytics, increasing autophagy, youthful blood factors exchange, and restoring cell polarity. Here, we review these strategies and their effects on rejuvenating stem cells in different tissues and underline when stem cell rejuvenation was able to improve health and lifespan.

Numerous links exist between stress granules (SGs) and neurodegenerative disease. When SGs cannot be properly cleared from the cell, they may become pathological and promote the aggregation of neurotoxic proteins. It is thus crucial that we understand the precise processes governing the degradation of SGs. Autophagy is a major mechanism mediating SG clearance, and autophagy dysfunction is a cardinal feature of neurodegenerative disease. In this review, we summarise current knowledge regarding the autophagy of SGs.

DNA methylation is an essential epigenetic mark associated with transcriptional silencing, but the mechanisms by which it controls gene expression remain elusive. Here, we review the pieces of evidence and molecular mechanisms linking the presence of DNA methylation with the activity of transcriptional enhancers. We discuss the implications on gene expression control in the context of the acquisition of cell identities during development.

RAN-binding protein 2 (RANBP2/Nup358) is a cytoplasmic filament nucleoporin involved in various cellular processes, such as nucleocytoplasmic transport and post-translational modifications. This review comprehensively discusses how dysregulation or mutation of RANBP2 contributes to human pathologies, and how the dynamic chromosomal region containing RANBP2 led to the appearance of the RANBP2 and GCC2 Protein Domains gene family during ape evolution.

Autophagy is a conserved intracellular degradation system in eukaryotes, involving the sequestration of degradation targets into autophagosomes. Autophagosome formation and cargo selectivity rely on core Atg proteins and cargo receptors, respectively. In this review, I cover the 30-year history of structural studies on core Atg proteins and cargo receptors and discuss the molecular mechanisms of autophagosome formation and selective autophagy.

Lipid droplets (LDs) are important for the storage of energy and lipid components. The perilipin family in mammals includes five proteins (PLIN1 to PLIN5), all of which are abundant on the surface of LDs in different tissues and play a role in LD stability and degradation by lipases. We discuss how perilipins interact with LDs, their function, and their implication in metabolic disease.

RNA-binding proteins (RBPs) associate with RNAs to regulate their functions and modulate diseases. Small molecules affecting the function of RBPs can be used in clinics. It is a challenging task to develop these molecules. Therefore, the strategies applicable for developing modulators of RBPs are described and accumulated studies prove the feasibility.

Irradiation of aqueous media with ultrasound produces combined chemical, mechanical, and thermal effects that are capable of affecting proteins at all organization levels from their primary to tertiary structure. Here, we summarize the progress made in understanding the structure and behavior-modifying impact of ultrasound on proteins focusing on their assembly/disassembly and discuss the effect of ultrasound on specific protein functionality.

Autophagy degrades or recycles cellular components through the formation of a double membrane vesicle, termed autophagosome, which fuses with the lysosome, where the degradation process takes place. In this Graphical Review we provide an updated and comprehensive overview on autophagosome biogenesis, a unique process consisting of three main phases: nucleation, expansion, and maturation, tightly regulated by lipid species and protein complexes.

We determined the structure of the human inner-arm dynein-d (IAD-d) stalk region, containing the microtubule-binding domain (MTBD) and coiled coil, by X-ray crystallography. Compared with the corresponding structures of other dyneins, we observed several unique structural features: the relative orientation of the coiled-coil and MTBD are different, and the orientation of the flap extending from the MTBD varies among axonemal dynein isoforms. We propose a structure-based model for IAD-d binding to microtubules.

Autophagy research in the past three decades has provided a detailed parts list of the initiation machinery. However, the regulation of its assembly and disassembly remains enigmatic. We summarize the role of HORMA domain proteins ATG13 and ATG101 in autophagosome biogenesis and explore how their hypothetical catalysed metamorphosis could be a responsive switch to conditionally activate autophagy initiation.

A bacterium and an autophagosome illustrated as dancing a Tango. This dance mirrors how autophagy and intracellular pathogens interact. (A) In specific instances, the autophagosome closely interacts with the partner, embracing the bacterium for engulfment and subsequent delivery into lysosomes for degradation. (B) In other cases, the bacterium responds and escapes from (avoid) the leader partner. These illustrations were created by Dr. Diego Croci, Group Leader at IHEM, CONICET, Argentina.

Fatty acids (FAs) are critical molecules for cell growth, proliferation, and development; but are toxic to cells when present in excess. Eukaryotic cells therefore sequester FAs in organelles called lipid droplets (LDs) until needed. LD synthesis and breakdown are under precise metabolic control, and dysregulation of these pathways is linked to lipotoxicity and diseases.

Seipin is a key factor in the assembly of lipid droplets at the endoplasmic reticulum. Here, we review recent advances provided by structural, biochemical, and in silico analyses that provided mechanistic insights into seipin function in lipid droplet formation.

Interactions between heterochromatin and the nuclear lamina are mediated by structural proteins that function to tether heterochromatin to the nuclear periphery. Here, we present an overview of the PRR14 chromatin tether, focusing on PRR14 protein structure and the mechanisms underlying PRR14 interactions with heterochromatin and the nuclear lamina in interphase and mitosis.

While 3% of lung cancers harbor mutations in exon 14 (Ex14) of the MET receptor, its oncogenic capabilities remain elusive, in particular the involvement of several regulatory sites in the juxtamembrane domain. The MET Y1003F mutation fully recapitulates the responses induced by MET exon 14 skipping, suggesting that loss of the CBL ubiquitin ligase binding site is the main factor in the cellular transformation induced by MET Ex14 mutations.

In this study, we investigated the functional significance of the C-terminal tail of the extracellular ATP receptor kinase, P2K1. We discovered that the C-terminal truncation of P2K1 led to extracellular ATP hypersensitivity and disruption of primary root growth and development. Our data suggest a crucial role for the C-terminal tail of P2K1 in regulating extracellular ATP signaling in plants.