Ali Turk

The fitness costs of reproductive specialization scale inversely with organismal size The evolution of reproductive specialization represents a fundamental innovation in multicellular life, yet the conditions favoring its evolution remain poorly understood. Here, we develop a populatio...

1/28 New preprint up, which I think is the best theoretical idea I've ever had. We asked a simple question: what are the costs of investment into non-reproductive somatic cells? Turns out these costs decrease with the *logarithm* of organism size!

www.biorxiv.org/content/10.6...

Plot showing metabolic rate and brain size vs. body mass. Warm-blooded animals expend an order of magnitude more energy and have brain sizes an order of magnitude larger

Soapbox time: the problem with metabolic efficiency arguments in neuroscience is that they often confuse energy efficiency with energy expenditure. Biological systems are optimized for energy efficiency, but that does NOT imply they are optimized for low energy expenditure 🧵 1/

Structure and mechanism of the mitochondrial calcium transporter NCLX - Nature Cryogenic electron microscopy structures and functional analyses reveal that NCLX functions as a H+/Ca2+ rather than a Na+/Ca2+ exchanger, and uncover its transport mechanism with implications for the...

Structure and mechanism of the mitochondrial calcium transporter NCLX.

A fin-loop-like structure in GPX4 underlies neuroprotection from ferroptosis: @cellpress.bsky.social www.cell.com/cell/fulltex...
www.cell.com/cms/10.1016/...

Innate immune and metabolic signals induce mitochondria-dependent membrane lysis via mitoxyperiosis Wang et al. identify a new lytic cell death pathway, mitoxyperilysis, triggered by the synergy of innate immune activation and metabolic stress. This process is regulated by mTORC2 and involves persis...

#NoTimeToDie! Welcome mitoxyperiosis! ⁦‪Kanneganti, Wang‬⁩ &co show ⁦‪@cp-cell.bsky.social that energy starvation via carbon deprivation in the presence of innate immune stimuli triggers a new form of cell death dependent on mitochondria-driven plasma membrane oxidative damage!

PANCS-spec-Binders: A system for rapidly discovering isoform- or epitope-specific binders Proteins that bind to a target protein of interest, termed "binders," are essential components of biological research reagents and therapeutics. Target proteins present multiple binding surfaces with ...

Check out our newest work! This is a story on how to get selectivity in binders - both isoform and site selectivity. Read the paper or enjoy this brief Skytorial of what we did!

www.biorxiv.org/content/10.1...

1/n

Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency - Nature Metabolism In a mouse model of the rare disease citrin deficiency, the authors discovered that the accumulation of glycerol-3-phosphate leads to ChREBP activation and FGF21 induction. The study identifies glycer...

www.nature.com/articles/s42...
Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in citrin deficiency

@charlesmbrenner.bsky.social congratulations!

An enzymatic cascade enables sensitive and specific proximity labeling proteomics in challenging biological systems - Nature Communications Proximity labeling allows proteomic mapping of subcellular structures. Here, Sroka et al. develop in situ APEX activation (iAPEX) to overcome limitations of labeling specificity and H2O2 toxicity, app...

Thrilled to share "in situ APEX activation" (iAPEX), a proximity labeling technology for subcellular #proteomics applied to primary #cilia. iAPEX uses an enzymatic cascade, in which a D-amino acid oxidase locally produces H2O2 to activate ascorbate peroxidase.
www.nature.com/articles/s41...

Proteome-wide in silico screening for human protein-protein interactions Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

Thrilled to share that the final piece of my PhD work is now on bioRxiv! biorxiv.org/content/10.1... With support from @nvidia and the @NSF, we used AlphaFold to screen 1.6M+ protein pairs, revealing thousands of potential novel PPIs. All data can be viewed at predictomes.org/hp

Cytosolic acetyl-coenzyme A is a signalling metabolite to control mitophagy - Nature Acetyl-coenzyme A functions as a non-canonical signal to trigger mitophagy, and the acetyl-coenzyme A–NLRX1 axis underlies the KRAS-inhibitor-induced mitophagy response and promotes drug resistan...

www.nature.com/articles/s41...
Cytosolic acetyl-coenzyme A is a signalling metabolite to control mitophagy

Arabidopsis AUGMIN8 Contains Two Independent Microtubule Association Domains Plant cells create a plasma membrane-associated network of microtubules that are nucleated by γ-tubulin ring complexes primarily through microtubule-dependent microtubule nucleation (MDMN). This dyna...

My first (and first-author) paper investigating how Arabidopsis AUGMIN8 interacts with microtubules is now available online in @cytoskeljournal.bsky.social! I'm incredibly grateful to have performed this work as an undergrad and postbac in Sidney Shaw's lab at IUB. doi.org/10.1002/cm.7...

ORP5 controls the partitioning of phosphatidic acid between triacylglycerol and cardiolipin synthesis at mitochondria-ER-lipid droplet contact sites https://www.biorxiv.org/content/10.1101/2025.11.06.685814v1

Excited to share our latest @nature.com: How does naloxone (Narcan) stop an opioid overdose? We determined the first GDP-bound μ-opioid receptor–G protein structures and found naloxone traps a novel "latent” state, preventing GDP release and G protein activation.💊🧪 🧵👇 www.nature.com/articles/s41...

Nature suggests you use their "Manuscript Adviser" bot to get advice before submitting

I uploaded the classic Watson & Crick paper about DNA structure, and the Adviser had this to say about one of the greatest paper endings of the century:

FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis - Nature Cell Biology Lange et al. identify a lipid droplet quality control pathway in which FSP1 safeguards stored neutral lipids from lipid peroxidation, thereby preventing the induction of ferroptosis.

Excited to share my postdoc work @olzmannlab.bsky.social! We found lipid droplets, the cell’s lipid storage depots, are subject to oxidative damage and are protected by FSP1. Loss of FSP1 triggers droplet peroxidation and cell death, revealing a new layer of lipid quality control!

shorturl.at/B5XYD

Molecular & Cellular Physiology (MCP) Monday

We are recruiting a tenure-track assistant professor to join the Dept of Molecular & Cellular Physiology at Stanford. Apply to be our colleague 1/n
facultypositions.stanford.edu/en-us/job/49...

Accumulation of succinate suppresses de novo purine synthesis through succinylation-mediated control of the mitochondrial folate cycle The de novo purine synthesis pathway is fundamental for nucleotide production, yet the role of mitochondrial metabolism in modulating this process rem…

Excited to share our latest work out today in @cp-molcell.bsky.social, revealing a molecular link between succinate dehydrogenase and purine synthesis, connecting two fundamental metabolic pathways. Huge congratulations to the first author, Mushtaq Nengroo! www.sciencedirect.com/science/arti...
!

A new, nerdy paper. We figured out (some) of the rules underlying cell-permeability of probes and designed ligands that light up, grab, and move proteins around. Awesome @hhmijanelia.bsky.social x @uwmadison.bsky.social x @stjuderesearch.bsky.social collaboration! www.pnas.org/doi/10.1073/...

Nematode telomerase RNA hitchhikes on introns of germline–up-regulated genes Telomerase is a ribonucleoprotein complex that elongates telomeric DNA, ensuring germline immortality. In this study, we identified the Caenorhabditis elegans telomerase RNA component 1 (terc-1), as t...

"Our findings uncovered a species survival strategy in which telomerase RNA extends telomeres for the next generation by hitchhiking on introns of germline-expressed genes." 🤯
#Celegans 🧪

T cell cholesterol transport links intestinal immune responses to dietary lipid absorption The intrinsic pathways that control membrane organization in immune cells and their impact on cellular functions are poorly defined. We found that the nonvesicular cholesterol transporter Aster-A link...

amazing #lipidtime story from Tontonoz lab! Lipid scrambling and cholesterol accessibility IN T-CELLS regulates nutrient uptake in small intestine 🤯🤯

Physiology is so weird!
www.science.org/doi/10.1126/...

An Inverse Electron-Demand Diels–Alder Approach to Selective Activity-Based Sensing of Acetaldehyde in Living Cells Acetaldehyde (AA) is a reactive aldehyde primarily produced in cells as a metabolic intermediate during ethanol oxidation. Excess AA, often resulting from impaired AA detoxification, leads to aberrant...

Excited to share work out in @jacs.acspublications.org led by Yuxuan and @genlichem.bsky.social on activity-based sensing of acetaldehyde using an inverse electron-demand Diels-Alder reaction, enabling selective detection of two-carbon metabolism! pubs.acs.org/doi/10.1021/...

You’ve heard of ubiquitination, meet deazaguanylation: Doug Wassarman in our lab discovered phage defense pathways have co-opted Q nucleobase biosynthetic enzymes to catalyze a new form of protein conjugation chemistry @science.org

www.science.org/doi/10.1126/...

Metal–Organic Frameworks from Edible Natural Products Let them eat MOFs: Take a spoonful of sugar (γ-cyclodextrin to be precise), a pinch of salt (most alkali metal salts will suffice), and a swig of alcohol (Everclear fits the bill), and you have a rob...

I don't have much intelligent things to say about MOFs other than "wow neat!" Also, there is an edible MOF paper: onlinelibrary.wiley.com/doi/abs/10.1...

#chemsky ⚗️🧪

KCTD10 is a sensor for co-directional transcription–replication conflicts @nature.com @mayoclinic.org
www.nature.com/articles/s41...

In vivo directed evolution of an ultrafast Rubisco from a semianaerobic environment imparts oxygen resistance | PNAS Carbon dioxide (CO2) assimilation by the enzyme Ribulose-1,5-bisphosphate Carboxylase/Oxygenase (Rubisco) underpins biomass accumulation in photosy...

www.pnas.org/doi/10.1073/...

How do cells sense & respond to lipid imbalances? What happens when a disease-relevant enzyme is blocked? Shiying Huang investigates phosphoinositide lipids with the Balla lab & discovers an integrated cellular response that boosts alternate lipid synthesis pathways! www.biorxiv.org/content/10.1...

Energy-transfer photoproximity labelling in live cells using an organic cofactor - Nature Chemistry Current photoproximity labelling methods often require metal-based catalysts to map protein interactomes but, owing to their toxicity, they have limited intracellular applicability. A deazaflavin cofa...

🔥After years of hard work, it's finally out in @natchem.nature.com🔥 The Hackenberger group @fmp-berlin.de developed #🎯DarT-labeling, a #photocatalyticproximitylabeling method using deazaflavin - a ✅ biocompatible ✅ easily synthesized ✅ chemically benign #photocatalyst

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

GCN1 couples GCN2 to ribosomal state to initiate amino acid response pathway signaling During nutrient deprivation, activation of the protein kinase GCN2 regulates cell survival and metabolic homeostasis. In addition to amino acid stress, GCN2 is activated by a variety of cellular stres...

Beautiful reconstitution of amino acid stress-dependent ISR activation by my @harvardcellbio.bsky.social colleagues presenting a unifying mechanism for GCN2 activation, which requires ribosome collisions and is enhanced by cognate uncharged tRNA in the A site! www.science.org/doi/10.1126/...

Indolequinone-Based Hypoxia-Activated Proteolysis Targeting Chimeras Selectively Degrade BRD4 in Hypoxic Cancer Cells Proteolysis targeting chimeras (PROTACs) have helped to establish proximity induction as an exciting strategy in drug discovery, and there are multiple clinical trials focused on this modality. Howeve...

Hypoxia-activated PROTACs (HAP-TACs) are online in @jacs.acspublications.org (pubs.acs.org/doi/10.1021/...)! Collborative work with Ester Hammond (@hammond-lab.bsky.social). Congrats to Marta Serafini, Sophie Twigger, George Delfas, Max Mallerman, Elliot Bailey & Ewen Calder (@ecalder.bsky.social).

Reprogramming neuroblastoma by diet-enhanced polyamine depletion - Nature Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

Reprogramming neuroblastoma by diet-enhanced polyamine depletion

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