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Lysosomal lipid metabolism promotes tumor cell invasion through local energetics and membrane lipid remodeling

Metabolic vulnerabilities in cancer have been targeted primarily to suppress tumor growth, but less is known about the metabolic requirements for tumor cell invasion. Here we report that lipid catabolism by cytosolic and lysosomal lipases supports pancreatic cancer cell invasion through both overlapping and distinct functional and metabolic mechanisms. Lysosomal acid lipase (LAL)-dependent lipid droplet catabolism promotes invadopodia formation and stabilization, enabling extracellular...

bioRxiv 4d ago

Human Genome-Scale Models of Metabolism and Gene Expression Reveal Resource Constraints of Cancer Cell Lines

Genome-scale metabolic models (M-models) provide mechanistic insight into intracellular metabolism by simulating fluxes subject to nutrient and energy resource constraints. However, they cannot account for a major component of resource allocation, since they do not explicitly account for the cost of producing and maintaining enzymes. Genome-scale models of metabolism and gene expression (ME-Models) address this by including gene expression reactions, but these have only been developed for...

bioRxiv 7d ago

Gut Microbiota Dysbiosis Drives Myocardial Hypertrophy Through GBP2b/GBP1-Mediated Immune Reprogramming and Exosomal Signaling in Chronic Colitis

BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk of cardiovascular disease, yet the mechanisms linking chronic intestinal inflammation to cardiac dysfunction remain poorly understood. IBD is characterized by profound gut microbiota dysbiosis, which we hypothesize drives systemic immune dysregulation and contributes to cardiac dysfunction. A chronic colitis mouse model was used to assess gut microbiota dysbiosis, systemic immune cell metabolism, and cardiac...

bioRxiv 10d ago

Anthocyanin-associated cellular programs underlying terroir variation in Cabernet Sauvignon grape berry revealed by SEED-based deconvolution

Plant tissues consist of diverse cell populations that collectively contribute to development, metabolism, environmental responses, and phenotype formation. Although single-cell and single-nucleus RNA sequencing have greatly advanced the study of plant cellular heterogeneity, their application to large sample cohorts remains limited by cost, technical complexity, tissue dissociation constraints, and throughput. In contrast, bulk RNA-seq datasets have accumulated extensively across plant...

bioRxiv 3d ago

Effects of ERK1/2 Signaling on Cell Cycle Regulation by the Tuberin-Cyclin B1 Complex

How cells balance growth (cell size) and division (cell number) requires a complex interplay between response to external signals, including growth factors, nutrient availability and metabolic cues, along with regulation of the cell cycle. The protein Tuberin (gene TSC2) is a critical regulator of these decisions. In a complex with the protein Hamartin, Tuberin functions as a negative regulator of the Target of Rapamycin (mTOR) pathway, preventing excessive growth under unfavorable conditions.

bioRxiv 3d ago

From flat moss to forests and flowers: Protein discovery may explain how plants conquered land

From flat moss to forests and flowers: Protein discovery may explain how plants conquered land Sadie Harley Scientific Editor Robert Egan Associate Editor If plants had never learned to grow in multiple directions, our world would look very different. No trees, flowers, or other complex plants—and therefore no animals or humans. New research from the University of Copenhagen now suggests that a specific protein in moss may have been crucial for this key step in plant evolution—a step that...

Phys.org 8d ago

Vacuole pH loss triggers ESCRT-dependent plasma membrane remodeling to prevent amino acid toxicity

Loss of lysosomal or vacuolar acidity is a hallmark of aging, metabolic dysfunction, and cellular stress, yet how cells adapt to this condition remains poorly understood. In budding yeast, where the vacuole serves as a major reservoir for intracellular amino acids, impaired vacuolar acidification disrupts amino acid homeostasis. Here we performed a genome-wide screen in budding yeast to identify pathways required for survival during vacuole pH stress.

bioRxiv 4d ago

The Dirt That Refused to Die

The Dirt That Refused To Die Introduction For 15 years, Sébastien Fontaine has been trying to kill dirt. The biochemist, who runs a lab at the French National Institute for Agriculture, Food, and Environment, wanted to know how much carbon is released by soil — just dirt alone, completely devoid of life. His team sealed dirt into jars and blasted them with sterilizing gamma radiation.

Hacker News 9d ago

Organ on chip model of respiratory vascular interactions under COPD relevant oxidative stress

Oxidative stress-induced airway injury contributes to chronic obstructive pulmonary disease (COPD). Cardiovascular complications increase COPD morbidity and mortality, but mechanistic links between airway injury and vascular dysfunction remain unclear, largely due to limitations of in vitro models that fail to replicate the multicellular lung environment. We developed REVAS, a modular organ-on-chip platform to study human respiratory-vascular cell-cell interactions at baseline and under...

bioRxiv 1d ago

Mitochondria directly interact with the nuclear pore complex

Abstract Mitochondria regulate cellular processes through direct and indirect interactions with other organelles. A well-studied example has been contact with the endoplasmic reticulum at mitochondrial-associated endoplasmic reticulum membranes1, which control pathways including redox and calcium homeostasis2,3. Recent studies have also reported direct mitochondria–nuclear membrane contacts in cancer cells and yeast that promote pro-survival signalling4,5.

Nature 17h ago