Biology subjects

Jaeger, C.

Publications and source records attributed to Jaeger, C..

At least 19 recordsLinked to original sources

bioRxiv2026

Evolution of the motor cortex microstructure and its lateralization: a comparative study of chimpanzees and humans

Human hand coordination exceeds that of other species, including great apes, and is marked by pronounced right-hand dominance. This specialization parallels an expansion of its cortical representation, forming the hand-knob in the motor cortex. In humans, this region shows high myelination on quantitative MRI (qMRI), but whether this feature is shared with great apes remains unclear. It is also unknown whether increased right-hand dominance in humans is mirrored by greater hemispheric asymmetry in cortical microstructure. Using high-resolution qMRI, we compared motor cortex subdivisions controlling the leg, hand, and face in humans and chimpanzees. We found consistently higher myelin and iron content in the hand-knob in both species, suggesting an evolutionarily conserved role. However, only humans showed enhanced rightward lateralization. These results highlight both conserved and species-specific features of the motor cortex, offering insights into the evolution of manual dexterity and handedness.

neuroscience↗

bioRxiv2025

Observations of anisotropic paramagnetic and diamagnetic susceptibility in the primate brain

Bulk magnetic susceptibility in the brain white matter is known to be diamagnetic and anisotropic due to the ordered myelin lipids. While paramagnetic iron is widely present in the brain, it is typically not considered to contribute to anisotropy. Using experimental MRI and computational techniques, this study explores the competing contribution of diamagnetic and paramagnetic substances to the susceptibility anisotropy. Multi-echo gradient-echo imaging and diffusion-weighted imaging data from a paraformaldehyde-fixed post-mortem chimpanzee (Pan troglodytes verus) brain was analyzed. A computational method, DECOMPOSE-QSM, was used to separate paramagnetic susceptibility and diamagnetic susceptibility components. As expected, diamagnetic components showed significant anisotropy; unexpectedly, paramagnetic components also exhibited strong anisotropy in deep gray matter and parts of white matter. This may arise from the geometric arrangement of iron-rich cellular compartments, such as oligodendrocytes, astrocytes, and microglia, along nerve fibers. This method enables further exploration of tissue-specific contributions to susceptibility anisotropy.

neuroscience↗

bioRxiv2024

Integrated multi-omics highlights alterations of gut microbiome functions in prodromal and idiopathic Parkinson's disease

Parkinsons disease (PD) is associated with gut microbiome shifts, but the functional consequences remain unclear. Here, we use an integrated multi-omics approach to compare the gut microbiomes of individuals with PD and prodromal PD as well as healthy individuals. After analyzing each omics, meta-metabolomic was selected to inform the analysis as it represents the most discriminatory and robust ome. We identified 11 metabolites that were differentially abundant between the groups, amongst which {beta}-glutamate was increased in PD and prodromal PD, and correlated with the transcriptional activities of Methanobrevibacter smithii and Clostridium spp. We identified decreases in transcripts, but not in gene abundances, related to glutamate metabolism, bile acids, chemotaxis and flagellar assembly in PD, particularly in keystone genera such as Roseburia, Agathobacter and Blautia. Our findings, integrated into the Expobiome map, reveal multifactorial microbiome alterations which converge with PD pathways. Our study highlights the importance of investigating the gut microbiomes functional dimensions to better resolve microbiome-host interactions in health and disease.

systems biology↗

bioRxiv2024

Lifespan trajectory of chimpanzee brains characterized by magnetic resonance imaging histology

Chimpanzee brain maturation provides an invaluable framework for understanding the evolution of the human brain. We performed ultra-high resolution quantitative magnetic resonance imaging (qMRI) with histological validation on post mortem brains from captive and wild chimpanzees with a broad age range. We mapped developmental myelination and age-related iron accumulation across regions and layers of the neocortex. Compared to humans, chimpanzees showed more myelination and iron deposition in motor and premotor cortices, while the auditory cortex was more strongly myelinated in humans. Our model suggests that chimpanzees cortical myelination was largely completed by the age of nine years, while iron accumulation continued throughout the lifespan. The regions with highest adult levels of myelin and iron took the longest to mature, challenging the widespread assumption that highly myelinated regions complete their development first. The reported maps and developmental curves provide a foundation for comparative neuroscience research and understanding of human brain evolution.

neuroscience↗

bioRxiv2024

The evolutionary path of the epithelial sodium channel delta-subunit in Cetartiodactyla points to a role in sodium sensing

The epithelial sodium channel (ENaC) plays a key role in osmoregulation in tetrapod vertebrates and is a candidate receptor for salt taste sensation. There are four ENaC subunits (, {beta}, {gamma}, {delta}) which form {beta}{gamma}- or {delta}{beta}{gamma} ENaCs. While {beta}{gamma}-ENaC is a maintenance protein controlling sodium and potassium homeostasis, {delta}{beta}{gamma}-ENaC might represent a stress protein monitoring high sodium concentrations. The {delta}-subunit emerged with water-to-land transition of tetrapod vertebrate ancestors. We investigated the evolutionary path of ENaC-coding genes in Cetartiodactyla, a group comprising even-toed ungulates and the cetaceans (whales/dolphins) which transitioned from terrestrial to marine environments in the Eocene. The genes SCNN1A (-ENaC), SCNN1B ({beta}-ENaC) and SCNN1G ({gamma}-ENaC) are intact in all 22 investigated cetartiodactylan families. While SCNN1D ({delta}-ENaC) is intact in terrestrial Artiodactyla, it is a pseudogene in 12 cetacean families. A fusion of SCNN1D exons 11 and 12 under preservation of the open reading frame was observed in the Antilopinae, representing a new feature of this clade. Transcripts of SCNN1A, SCNN1B and SCNN1G were present in kidney and lung tissues of Bottlenose dolphins, highlighting {beta}{gamma}-ENaCs role as a maintenance protein. Consistent with SCNN1D loss, Bottlenose dolphins and Beluga whales did not show behavioural differences to stimuli with or without sodium in seawater-equivalent concentrations. These data suggest a function of {delta}-ENaC as a sodium sensing protein which might have become obsolete in cetaceans after the migration to high-salinity marine environments. Consistently, there is reduced selection pressure or pseudogenisation of SCNN1D in other marine mammals, including sirenians, pinnipeds and sea otter.

evolutionary biology↗

bioRxiv2024

DJ-1 mediates regulation of metabolism and immune response in Parkinsons disease astrocytes and Glioblastoma cells

An inverse correlation for the expression of Parkinsons disease (PD)- and cancer-associated genes has been previously reported. Genes that are upregulated in cancer are frequently downregulated in PD and vice versa. PARK7, encoding DJ-1, was initially identified as an oncogene, but loss of DJ-1 causes early-onset PD. However, it remains elusive how differential DJ-1 levels contribute to opposite cell fates in cancer and PD. Here, we demonstrate specific effects of differential DJ-1 protein levels on the energy metabolism and cell growth in patient-derived cellular models of PD and glioblastoma (GBM) cell lines. Impaired energy metabolism was associated with an increased immune response upon IL-1{beta} stimulation and increased apoptosis and decreased cell growth in models of PD, whereas in GBM cells increased metabolic activity translated into a reduced immune response and increased cell growth. Furthermore, we found decreased glutathione (GSH) synthesis and therefore increased levels of reactive oxygen species (ROS) and oxidized glutathione (GSSG) in models of DJ-1 deficiency and decreased ROS levels in GBM cell lines. Thus, the mechanism by which DJ-1 modulates these phenotypes is the same in both diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/621212v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@4eccb4org.highwire.dtl.DTLVardef@161669corg.highwire.dtl.DTLVardef@197bfc3org.highwire.dtl.DTLVardef@1aecb36_HPS_FORMAT_FIGEXP M_FIG C_FIG DJ-1 levels modulate GSSG/GSH ratio and ROS levels, which results in divergent effects on cell growth and immune response in DJ-1-dependent glial pathologies in glioblastoma and PD. In models of PD, DJ-1 level dependent phenotypes can be rescued by antioxidant treatment that reduces the GSSG/GSH ratio and ROS levels.

neuroscience↗

bioRxiv2024

Insulin resistance compromises midbrain organoid neural activity and metabolic efficiency predisposing to Parkinsons disease pathology

Growing evidence indicates that Type 2 Diabetes (T2D) is associated with an increased risk of developing Parkinsons disease through shared disease mechanisms. Studies show that insulin resistance, which is the driving pathophysiological mechanism of T2D plays a major role in neurodegeneration by impairing neuronal functionality, metabolism, and survival. To investigate insulin resistance caused pathological changes in the human midbrain, which could predispose a healthy midbrain to PD development, we exposed iPSC-derived human midbrain organoids from healthy individuals to either high insulin concentrations, promoting insulin resistance, or to more physiological insulin concentrations restoring insulin signalling function. We combined experimental methods with metabolic modelling to identify the most insulin resistance-dependent pathogenic processes. We demonstrate that insulin resistance compromises organoid metabolic efficiency, leading to increased levels of oxidative stress. Additionally, insulin-resistant midbrain organoids showed decreased neural activity and reduced amount of dopaminergic neurons, highlighting insulin resistance as a significant target in PD prevention.

neuroscience↗

bioRxiv2023

CLN3 deficiency leads to neurological and metabolic perturbations during early development

Juvenile Neuronal Ceroid Lipofuscinosis (or Batten disease) is an autosomal recessive, rare neurodegenerative disorder that affects mainly children above the age of 5 years and is most commonly caused by mutations in the highly conserved CLN3 gene. Here, we generated cln3 morphants and stable mutant lines in zebrafish. Although neither morphant nor mutant cln3 larvae showed any obvious developmental or morphological defects, behavioral phenotyping of the mutant larvae revealed higher basal activity, hyposensitivity to abrupt light changes and hypersensitivity to pro-convulsive drugs. Importantly, in-depth metabolomics and lipidomics analyses revealed significant accumulation of several glycerophosphodiesters (GPDs) and a global decrease of bis(monoacylglycero)phosphate (BMP) species, two classes of molecules previously proposed as potential biomarkers for CLN3 disease based on independent studies in other organisms. We could also demonstrate GPD accumulation in human-induced pluripotent stem cell-derived cerebral organoids carrying a pathogenic variant for CLN3. Our models revealed that GPDs accumulate at very early stages of life in the absence of functional CLN3 and highlight glycerophosphoinositol and BMP as promising biomarker candidates for pre-symptomatic CLN3 disease.

molecular biology↗

bioRxiv2023

PKM2 diverts glycolytic flux in dependence on formate overflow

Throughout the metastatic cascade, cancer cells are faced with harsh metabolic environments and nutritional stresses which apply selection pressure leaving only the most metabolically resilient cells to survive and form metastases. Metabolic characterisation of such cell populations in vitro is currently challenging. Using galactose as a tool compound to mimic glycolytic limitation within the tumour microenvironment of primary and secondary neoplastic sites, we were able to uncover metabolic flexibility and plasticity of cancer cells in vitro. In contrast to the established idea that high glycolytic flux and expression of dimeric PKM2 redirects carbons towards anabolic routes such as the pentose phosphate pathway and serine synthesis pathway (SSP), we have discovered by using stable-isotope tracing that also glycolytic limitation results in metabolic rewiring. Surprisingly, despite limited carbon availability and energetic stress, cells induce a near complete block of pyruvate kinase isozyme M2 (PKM2) to divert carbons towards SSP. Simultaneously, TCA cycle flux is sustained and oxygen consumption is increased, both supported by glutamine. Glutamine not only supports TCA cycle flux but also SSP via distinct mechanisms. Due to PKM2 block, malic enzyme exclusively supports TCA cycle flux while mitochondrial phosphoenolpyruvate carboxykinase supports SSP. Moreover, by using genetic modifications of different one-carbon (1C) cycle enzymes, we are able to reverse the PKM2 block suggesting a link between mitochondrial 1C cycle and pyruvate kinase. Thus we show that PKM2 inhibition acts as a branching point to direct glycolytic and glutamine carbons into distinct routes, overall supporting the metabolic plasticity and flexibility of cancer cells.

cancer biology↗

bioRxiv2023

Formate Promotes Invasion and Metastasis by Activating Fatty Acid Synthesis and Matrix Metalloproteinases

Metabolic rewiring is essential to enable cancer onset and progression. One important metabolic pathway that is often hijacked by cancer cells is the one-carbon cycle, in which the third carbon of serine is oxidized to formate. We have previously shown that formate production in cancer cells often exceeds the anabolic demand, resulting in formate overflow. Furthermore, we observed that high extracellular formate promotes the in vitro invasiveness of glioblastoma (GBM) cells. However, additional data supporting this in vitro observation and mechanistic details remained elusive so far. In the present study, we now demonstrate that inhibition of formate overflow results in a decreased invasiveness of GBM cells ex vivo and in vivo. Additionally, we observed that exposure to exogeneous formate can induce a transiently stable pro-invasive phenotype that results in increased metastasis formation in vivo. All in all, these results suggest that a local formate increase within the tumor microenvironment may be one factor that can promote cancer cell motility and dissemination. Mechanistically, we uncover a previously undescribed interplay where formate acts as a trigger to alter fatty acid metabolism and matrix metalloproteinase (MMP) activity which in turn impacts cancer cell invasiveness. We thus highlight the role of formate as a pro-invasive metabolite. Gaining a deeper understanding of formate overflow and how it promotes invasion in cancer, may open new therapeutic opportunities to prevent cancer cell dissmination.

cancer biology↗

bioRxiv2022

Steroidogenesis and androgen/estrogen signaling pathways are altered in in vitro matured testicular tissues of prepubertal mice

Children undergoing cancer treatments are at risk for impaired fertility. Cryopreserved prepubertal testicular biopsies could theoretically be later matured in vitro to produce spermatozoa for assisted reproductive technology. A complete in vitro spermatogenesis has been obtained from mouse prepubertal testicular tissue, although with low efficiency. Steroid hormones being essential for the progression of spermatogenesis, the aim of this study was to investigate steroidogenesis and steroid signaling in organotypic cultures. Histological, RT-qPCR, western blot analyses and steroid hormone measurements were performed on in vitro cultured mouse prepubertal testicular tissues and age-matched in vivo controls. Despite a conserved density of Leydig cells after 30 days of culture (D30), transcript levels of adult Leydig cell and steroidogenic markers were decreased. Increased amounts of progesterone and estradiol and reduced androstenedione levels were observed at D30, together with decreased transcript levels of steroid metabolizing genes and steroid target genes. hCG was insufficient to facilitate Leydig cell differentiation, restore steroidogenesis and improve sperm yield. In conclusion, this study reports the failure of adult Leydig cell development and altered steroid production and signaling in tissue cultures. The organotypic culture system will need to be further improved before it can be translated in clinics for childhood cancer survivors.

developmental biology↗

bioRxiv2022

High Angular Resolution Susceptibility Imaging and Estimation of Fiber Orientation Distribution Functions in Primate Brain

Uncovering brain-tissue microstructure including axonal characteristics is a major neuroimaging research focus. Within this scope, anisotropic properties of magnetic susceptibility in white matter have been successfully employed to estimate primary axonal trajectories using mono-tensorial models. However, anisotropic susceptibility has not yet been considered for modeling more complex fiber structures within a voxel, such as intersecting bundles, or an estimation of orientation distribution functions (ODFs). This information is routinely obtained by high angular resolution diffusion imaging (HARDI) techniques. In applications to fixed tissue, however, diffusion-weighted imaging suffers from an inherently low signal-to-noise ratio and limited spatial resolution, leading to high demands on the performance of the gradient system in order to mitigate these limitations. In the current work, high angular resolution susceptibility imaging (HARSI) is proposed as a novel, phase-based methodology to estimate ODFs. A multiple gradient-echo dataset was acquired in an entire fixed chimpanzee brain at 61 orientations by reorienting the specimen in the magnetic field. The constant solid angle method was adapted for estimating phase-based ODFs. HARDI data were also acquired for comparison. HARSI yielded information on whole-brain fiber architecture, including identification of peaks of multiple bundles that resembled features of the HARDI results. Distinct differences between both methods suggest that susceptibility properties may offer complementary microstructural information. These proof-of-concept results indicate a potential to study the axonal organization in post-mortem primate and human brain at high resolution. HighlightsO_LIIntroduction of High Angular Resolution Susceptibility Imaging (HARSI) for advancing Quantitative Susceptibility Mapping (QSM). C_LIO_LIHARSI-derived fiber orientation distributions in fixed chimpanzee brain. C_LIO_LIHARSI-based visualization of complex fiber configurations. C_LIO_LIComparisons between HARSI and High Angular Resolution Diffusion Imaging. C_LIO_LIPotential for high-resolution post-mortem imaging of fiber architecture. C_LI

neuroscience↗

bioRxiv2022

B1+-correction of MT saturation maps optimized for 7T postmortem MRI of the brain

PurposeMagnetization transfer saturation (MTsat) is a useful marker to probe tissue macromolecular content and myelination in the brain. The increased [Formula] -inhomogeneity at [≥] 7T and significantly larger saturation pulse flip angles which are often used for postmortem studies exceed the limits where previous MTsat [Formula] correction methods are applicable. Here, we develop a calibration-based correction model and procedure, and validate and evaluate it in postmortem 7T data of whole chimpanzee brains. TheoryThe [Formula] dependence of MTsat was investigated by varying the off-resonance saturation pulse flip angle. For the range of saturation pulse flip angles applied in typical experiments on postmortem tissue, the dependence was close to linear. A linear model with a single calibration constant C is proposed to correct bias in MTsat by mapping it to the reference value of the saturation pulse flip angle. MethodsC was estimated voxel-wise in five postmortem chimpanzee brains. "Individual-based global parameters" were obtained by calculating the mean C within individual specimen brains and "group-based global parameters" by calculating the means of the individual-based global parameters across the five brains. ResultsThe linear calibration model described the data well, though C was not entirely independent of the underlying tissue and [Formula]. Individual-based and group-based global correction parameters (C = 1.2) led to visible, quantifiable reductions of [Formula]-biases in high resolution MTsat maps. ConclusionThe presented model and calibration approach effectively corrects for [Formula] in-homogeneities in postmortem 7T data.

neuroscience↗

bioRxiv2022

Adaptation to ER-stress via serine glycine metabolism licences STING signalling and CMV control in intestinal epithelial cells

Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract. While the molecular causality between endoplasmic reticulum (ER) stress and intestinal inflammation is widely accepted, the metabolic consequences of chronic ER-stress on the pathophysiology of IBD remain unclear. By using in vitro, ex vivo, in vivo mouse models and patient datasets, we identified a distinct polarisation of the mitochondrial one-carbon (1C) metabolism and a fine-tuning of the amino acid uptake in intestinal epithelial cells tailored to support GSH and NADPH metabolism upon chronic ER-stress. This metabolic phenotype strongly correlates with IBD severity and therapy-response. Mechanistically, we uncover that both chronic ER-stress and serine limitation disrupt cGAS/STING-signalling, impairing the epithelial response against viral and bacterial infection, fuelling experimental enteritis. Consequently, antioxidant treatment restores STING function and virus control. Collectively, our data highlight the importance of the plasticity of serine metabolism to allow proper cGAS/STING-signalling and innate immune responses upon chronic inflammation in the gut.

cell biology↗

bioRxiv2022

Deciphering the fibre-orientation independent component of R2* (R2,iso*) in the human brain with a single multi-echo gradient-recalled-echo measurement under varying microstructural conditions

The effective transverse relaxation rate (R2*) is sensitive to the microstructure of the human brain, e.g. the g-ratio characterising the relative myelination of axons. However, R2* depends on the orientation of the fibres relative to the main magnetic field degrading its reproducibility and that of any microstructural derivative measure. To decipher its orientation-independent part (R2,iso*), a second-order polynomial in time (M2) can be applied to single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientation. The linear-time dependent parameter, {beta}1, of M2 can be biophysically related to R2,iso* when neglecting the signal from the myelin water (MW) in the hollow cylinder fibre model (HCFM). Here, we examined the effectiveness of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We showed that the fitted {beta}1 effectively estimates R2,iso*when using meGRE with long maximum echo time (TEmax {approx} 54 ms) but its microscopic dependence on the g-ratio was not accurately captured. This error was reduced to less than 12% when accounting for the MW contribution in a newly introduced biophysical expression for {beta}1. We further used this new expression to estimate the MW fraction (0.14) and g-ratio (0.79) in a human optic chiasm. However, the proposed method failed to estimate R2,iso* for a typical in-vivo meGRE protocol (TEmax {approx} 18 ms). At this TEmax and around the magic angle, the HCFM-based simulations failed to explain the R2*-orientation-dependence. In conclusion, estimation of R2,iso* with M2 in vivo requires meGRE protocols with very long TEmax {approx} 54 ms.

neuroscience↗

bioRxiv2021

Synaptic decline precedes dopaminergic neuronal loss in human midbrain organoids harboring a triplication of the SNCA gene

1.Increased levels of the protein alpha-synuclein (-syn) are associated with the development of neurodegenerative diseases like Parkinsons disease (PD). In physiological conditions, -syn modulates synaptic plasticity, neurogenesis and neuronal survival. However, its pathogenic accumulation and aggregation results in toxicity and neurodegeneration. Here, we used a PD patient specific midbrain organoid model derived from induced pluripotent stem cells harboring a triplication in the SNCA gene to study PD-associated phenotypes. The model recapitulates the two main hallmarks of PD, which are -syn aggregation and loss of dopaminergic neurons. Additionally, impairments in astrocyte differentiation were detected. Transcriptomics data indicate that synaptic function is impaired in PD specific midbrain organoids. This is further confirmed by alterations in synapse number and electrophysiological activity. We found that synaptic decline precedes neurodegeneration. Finally, this study substantiates that patient specific midbrain organoids allow a personalized phenotyping, which make them an interesting tool for precision medicine and drug discovery.

neuroscience↗

bioRxiv2021

A representative reference for MRI-based human axon radius assessment using light microscopy

Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data on the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the frequency-weighted arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the potential error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (normalized-root-mean-square-error of reff: 7.2 %; rarith: 21.5 %) and lower bias (normalized-mean-bias-error of reff: -1.7 %; rarith: 16 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.9 % and 3 % to reff. In conclusion, the proposed method accurately estimates reff at MRI voxel resolution across a human corpus callosum sample. Further investigations are required to assess generalization to brain areas with different axon radii ensembles.

neuroscience↗

bioRxiv2021

Mitochondrial One-Carbon Flux has a Growth-Independent Role in Promoting Breast Cancer Metastasis

Progression of primary cancer to metastatic disease is the most common cause of death in cancer patients with minimal treatment options available. Canonical drugs target mainly the proliferative capacity of cancer cells, which often leaves slow-proliferating, persistent cancer cells unaffected. Metabolic determinants that contribute to growth-independent functions supporting resistance and metastatic dissemination are still poorly understood. In the present study, we revealed that antifolate treatment results in an uncoupled and autarkic mitochondrial one-carbon (1C) metabolism allowing sustained serine catabolism and formate overflow when cytosolic 1C metabolism is impaired. Interestingly, antifolate dependent growth-arrest did not correlate with decreased migration capacity. Therefore, using the antifolate Methotrexate as a tool compound allowed us to disentangle proliferation and migration to profile the metabolic phenotype of migrating (growth-arrested) cells. Supported by an increased NAD/NADH ratio, we observed increased serine de novo synthesis and increased serine catabolism to formate. Consequently, inhibition of serine de novo synthesis using the competitive PHGDH-inhibitor BI-4916 or direct inhibition of mitochondrial 1C metabolism reduced cancer cell migration. Using an orthotopic breast cancer model, we show that sole inhibition of mitochondrial serine catabolism does not affect primary tumor growth but strongly inhibits pulmonary metastasis. We conclude that mitochondrial 1C metabolism, despite being dispensable for proliferative capacities, confers an advantage to cancer cells by supporting their motility potential. Our results improve our understanding of 1C metabolism and of metabolic determinants that support the process of cancer cell migration and metastasis.

cancer biology↗