In this study, using a combination of quantitative biochemical assays and fluorescence microscopy, the authors demonstrate that a fraction of free extracellular mitochondria can enter recipient cells through macropinocytosis. Once internalized, mitochondria are able to escape from endosomal compartments into the cytosol, where they may integrate into the endogenous mitochondrial network.

The authors uncovered channeled pyrimidine de novo biosynthesis and the preferential utilization of mitochondrially generated aspartic acid for pyrimidinosome and the purinosome mediated channeled pyrimidine and purine synthesis, respectively.

Khan et al. apply machine learning to identify substrates of UNC93A, SLC45A4, and SLC25A45. Biochemical assays and in vivo metabolite tracing establish SLC25A45 as a key mediator of mitochondrial impo...

Methylated amino acids accumulate upon the degradation of methylated proteins and are implicated in diverse metabolic and signaling pathways. Disturbe…

We appoint researchers from across biology and biomedicine to set up their first groups at the Crick.

As biomedical research prioritizes human models and translational promise, classic model organisms are increasingly dismissed. Here we argue that they have a lasting value, both in enabling discovery and in cultivating scientific thinking, by training researchers in systems reasoning, integrative thinking and independent inquiry.

Park, Nicaise, Tsitsipatis, and colleagues discover transcriptional and epigenetic markers in human PMS iNSCs and fibroblasts that may underlie their senescent and inflammatory state. Novel DARGs with...

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that na...

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that naked mole-rat cyclic guanosine monophosphate–adenosine ...

Mitochondrial synthesis of adenosine triphosphate is essential for eukaryotic life but is dependent on the cooperation of two genomes: nuclear and mitochondrial DNA (mtDNA). mtDNA mutates ~15 times as...

Unbiased clustering analysis of the skeletal muscle RNAome in patients with cancer identifies two molecular subtypes, one of which distinguishes individuals with cachexia and indicates potential target pathways for future research.

Garone and colleagues explore the potential of gene therapy and mRNA drugs in treating mitochondrial disorders, reviewing in vivo and in vitro models. They emphasize the challenges that remain to be a...

Designing good research questions goes well beyond the standard definitions of clarity, focus and tractability, and even beyond ‘novelty’ in the strictest sense. This Comment describes the iterative creative process for designing good research questions, and includes practical suggestions and ways to avoid common traps.

The extracellular space is a critical environment for discriminating self versus non-self nucleic acids and initiating the appropriate immune responses through signaling cascades to relay information ...

In 1985, experiments revealed the quantum behaviour of a macroscopic degree of freedom: the phase difference across a Josephson junction. The authors recount the history of this milestone for the development of superconducting quantum circuits.

This Review by Imianowski et al. outlines the various contributions that regulatory T cells, present in the tumour microenvironment, make towards tumour progression and highlight the ways in which they represent attractive next-generation immunotherapeutic targets.