RyanLab_TCD

Quantitative cellular characterization of extracellular mitochondria uptake and delivery - Nature Communications 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.

Quantitative cellular characterization of extracellular mitochondria uptake and delivery #mitochondria #transfer
www.nature.com/articles/s41...

📢Last weeks #immunometabolism discoveries @biomednews.bsky.social ⬇️⬇️⬇️

biomed.news/bims-imicid/...

Many highlights inside!

incl. TRAF6 integrates innate immune signals to regulate glucose homeostasis via Parkin-dependent and Parkin-independent mitophagy

Metabolic profiling reveals channeled de novo pyrimidine and purine biosynthesis fueled by mitochondrially generated aspartic acid in cancer cells - Nature Communications 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.

Metabolic profiling reveals channeled de novo pyrimidine and purine biosynthesis fueled by mitochondrially generated aspartic acid in cancer cells
www.nature.com/articles/s41...

Good Sunday, all. Your weekly curated summary of papers in #cancermetabolism and #mitochondrialbiology is ready, don't miss it as it is full of exceptional discoveries: biomed.news/bims-camemi/... Biomed News #keepreading

"To see takes time, like to have a friend takes time." -Georgia O'Keeffe

Machine-learning-guided discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine synthesis 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...

Excited to share our work on discovery of SLC25A45 as a mediator of mitochondrial methylated amino acid import and carnitine biosynthesis. @cp-cellmetabolism.bsky.social www.cell.com/cell-metabol...

SLC25A45 is required for mitochondrial uptake of methylated amino acids and de novo carnitine biosynthesis Methylated amino acids accumulate upon the degradation of methylated proteins and are implicated in diverse metabolic and signaling pathways. Disturbe…

A brilliant new paper by @Marilia Meira Dias and @Thomas MacVicar and others is out! It has discovered that a mitochondrial carrier SLC25A45 is involved in the uptake of methylated lysine and arginine, a key step in carnitine biosynthesis!

www.sciencedirect.com/science/arti...

Congratulations Sara and to the team! Exciting to have the first paper out!

Whoo hoo! The final version of our first paper is online! So proud of the team. kwnsfk27.r.eu-west-1.awstrack.me/L0/https:%2F...

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

The @crick.ac.uk is recruiting Early Career Group Leaders

- Lab set-up, research costs, salaries for up to 5 researchers
- Support for up to 12 years
- Access to our core facilities
- Competitive salary
- Fantastic colleagues
- All areas of biology

Deadline 27 Nov

www.crick.ac.uk/careers-stud...

Reaffirming the value of model organisms in training scientific minds - Nature Cell Biology 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.

PREACH!

www.nature.com/articles/s41...

mitochondria from bipolar patients are closer to the nucleus in these images; control patients' are spread out further

15 years in the making, we confirmed that mitochondria - the powerhouse of the cell - have an unusual localization in patients who experience psychosis (including schizophrenia and bipolar disorders). You’ll never guess what kind of patient cells we used to make this discovery… 🧵

Integrated omics reveals disease-associated radial glia-like cells with epigenetically dysregulated interferon response in multiple sclerosis 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...

Delighted to see this out in @NeuroCellPress!!!

Together with Isabel Beerman (& many other friends) we identify disease-associated radial glia-like cells (#DARGs) that fuel #inflammation and #neurodegeneration in #progressiveMS

www.cell.com/neuron/fullt...

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging 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...

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging | Science www.science.org/doi/10.1126/...

😂😂

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging 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 ...

A cGAS-mediated mechanism in naked mole-rats potentiates DNA repair and delays aging

Naked mole rats get much older than closely related mamals of a similar size. cGAS mutations may have an important role in this.

www.science.org/doi/...
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We're now recruiting early career group leaders at the Crick to lead ambitious research programmes and explore bold scientific questions.

Hear our Director, Edith Heard, explain why the Crick is a unique place for curiosity-driven research.

Apply now ➡️ www.crick.ac.uk/careers-stud...

Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations 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...

Exciting study from @frisophagy.bsky.social in @chinnery in the Chinnery lab @mrc-mbu.bsky.social. Congratulations to all authors involved in the study! #mitochondria

Ubiquitin-mediated mitophagy regulates the inheritance of mitochondrial DNA mutations | Science
www.science.org/doi/10.1126/...

Molecular subtypes of human skeletal muscle in cancer cachexia - Nature 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.

www.nature.com/articles/s41...

Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies 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...

Gene therapy and mRNA drugs approach for mitochondrial OXPHOS deficiencies: Molecular Therapy www.cell.com/molecular-th...

How to develop good research questions - Nature Human Behaviour 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.

www.nature.com/articles/s41...

Temporal and context-dependent requirements for the transcription factor Foxp3 expression in regulatory T cells @natimmunol.nature.com @yuripritykin.bsky.social Rudensky @princetonupress.bsky.social @mskcancercenter.bsky.social www.nature.com/articles/s41...

DNASE1L3 surveils mitochondrial DNA on the surface of distinct mammalian cells 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 ...

We’re excited to report work led by postdoc Jennifer Porat in the lab, finding that DNA accumulates on the surface of living cells and that the secreted extracellular protein DNASE1L3 can modulate its levels on B and T cells. With a new twist for ATAC-seq as well www.biorxiv.org/content/10.1...

#goals

Quantum Josephson junction circuits and the dawn of artificial atoms - Nature Physics 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.

Want to read a Comment by the three Nobel Laureates on quantum circuits?

Here it is: ($)

www.nature.com/articles/s41...

Regulatory T cells in the tumour microenvironment - Nature Reviews Cancer 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.

Dr Sakaguchi first identified regulatory T (Treg) cells, which have a crucial role in protecting the body against immune attack and thus preventing autoimmune disease. They also play an important role in cancer, as discussed in our recent review 👇

bit.ly/438HiMV

It was completely serendipitous that my #immunometabolism highlight this week highlighting Tregs coincided with the Nobel Treg award 🔽🔽🔽 I swear I don't have any insights into the mysterious Nobel selection process.....

Varicella-zoster virus reactivation and the risk of dementia Nature Medicine - Large-scale longitudinal health records reveal consistent association of varicella-zoster virus reactivation with dementia.

Varicella-zoster virus reactivation and the risk of dementia

Vaccination is more that protection against the pathogen-caused disease.

www.nature.com/artic...
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Check out a lovely bitesize historical perspective from Adrian below.

Pre- and postantibiotic epoch: The historical spread of antimicrobial resistance Plasmids are now the primary vectors of antimicrobial resistance, but our understanding of how human industrialisation of antibiotics influenced their evolution is limited by a paucity of data predati...

Imagine we could travel back in time ⏪⌛️to explore the world of bacterial pathogens before humans discovered and industrialised antibiotics

We just did that to study the history of #AMR spread @science.org
doi.org/10.1126/scie...

If you like time travel & biology, this 🧵is for you👇

Paternal exercise confers endurance capacity to offspring through sperm microRNAs Yin et al. show that paternal exercise improves offspring endurance capacity and metabolic health via sperm microRNAs that reprogram gene expression in early embryos, revealing how exercise benefits c...

Exercising fathers, enhanced endurance and metabolic heath in offspring, through sperm microRNAs (as demonstrated in mice)
www.cell.com/cell-metabol...