Arrayed CRISPRi library to suppress genes required for Schizosaccharomyces pombe viability DOI
Ken Ishikawa, Saeko Soejima, T. Nishimura

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 224(1)

Published: Oct. 8, 2024

The fission yeast, Schizosaccharomyces pombe, is an excellent eukaryote model organism for studying essential biological processes. Its genome contains ∼1,200 genes cell viability, most of which are evolutionarily conserved. To study these genes, resources enabling conditional perturbation target required. Here, we constructed comprehensive arrayed libraries plasmids and strains to knock down in S. pombe using dCas9-mediated CRISPRi. These cover ∼98% all yeast. We estimate that ∼60% strains, transcription a gene was repressed so efficiently proliferation significantly inhibited. demonstrate the usefulness libraries, performed metabolic analyses with knockdown revealed flexible interaction among pathways. Libraries established this enable functional will facilitate understanding processes eukaryotes.

Language: Английский

What fuels the fly: Energy metabolism in Drosophila and its application to the study of obesity and diabetes DOI Creative Commons
Nirmalya Chatterjee, Norbert Perrimon

Science Advances, Journal Year: 2021, Volume and Issue: 7(24)

Published: June 9, 2021

Drosophila is a useful model system to study the regulation of energy metabolism and its diseases like obesity diabetes.

Language: Английский

Citations

154
Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice DOI Creative Commons
Ying Liu, Ezequiel Dantas, Miriam Ferrer

et al.

Nature Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Abstract Cachexia, a severe wasting syndrome characterized by tumour-induced metabolic dysregulation, is leading cause of death in people with cancer, yet its underlying mechanisms remain poorly understood. Here we show that longitudinal full-body single-nuclei-resolution transcriptome analysis Drosophila model cancer cachexia captures interorgan dysregulations. Our study reveals the tumour-secreted interleukin-like cytokine Upd3 induces fat-body expression Pepck1 and Pdk , key regulators gluconeogenesis, disrupting glucose metabolism contributing to cachexia. Similarly, mouse models, observe IL-6–JAK–STAT-signalling-mediated induction Pck1 Pdk3 liver. Increased these genes fly, mouse, human correlates poor prognosis, hepatic emerges as previously unknown mechanism dysfunction This highlights conserved nature disruptions identifies potential therapeutic targets mitigate cancer.

Language: Английский

Citations

1
The Drosophila model to interrogate triacylglycerol biology DOI Creative Commons
Christoph Heier,

Svitlana Klishch,

Olha Stilbytska

et al.

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2021, Volume and Issue: 1866(6), P. 158924 - 158924

Published: March 12, 2021

The deposition of storage fat in the form triacylglycerol (TAG) is an evolutionarily conserved strategy to cope with fluctuations energy availability and metabolic stress. Organismal TAG specialized adipose tissues provides animals a reserve that sustains survival during development starvation. On other hand, excessive accumulation TAG, defined as obesity, associated increasing prevalence human diseases. During past decade, fruit fly Drosophila melanogaster, traditionally used genetics developmental biology, has been established versatile model system study metabolism etiology lipid-associated Similar humans, homeostasis relies on interplay organ systems lipid uptake, synthesis, processing, which are integrated by endocrine network hormones messenger molecules. Enzymatic formation from sugar or dietary lipid, its droplets, mobilization lipolysis occur via mechanisms largely between humans. Notably, dysfunctional occurs context aging, overnutrition, defective gene function, entails tissue-specific organismal pathologies resemble disease. In this review, we summarize physiology biochemistry outline potential organism understand genetic basis TAG-related disorders.

Language: Английский

Citations

41
Energy metabolic pathways in neuronal development and function DOI Creative Commons
Sebastian Rumpf,

Neeraja Sanal,

Marco Marzano

et al.

Oxford Open Neuroscience, Journal Year: 2023, Volume and Issue: 2

Published: Jan. 1, 2023

Abstract Neuronal development and function are known to be among the most energy-demanding functions of body. Constant energetic support is therefore crucial at all stages a neuron’s life. The two main adenosine triphosphate (ATP)-producing pathways in cells glycolysis oxidative phosphorylation. Glycolysis has relatively low yield but provides fast ATP enables metabolic versatility needed dividing neuronal stem cells. Oxidative phosphorylation, on other hand, highly efficient thought provide or differentiated neurons. However, it recently become clear that due their distinct properties, both required fully satisfy energy demands during function. Here, we an overview how phosphorylation used neurons

Language: Английский

Citations

16
A high-protein diet-responsive gut hormone regulates behavioral and metabolic optimization in Drosophila melanogaster DOI Creative Commons
Yuto Yoshinari, T. Nishimura, Taishi Yoshii

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 30, 2024

Protein is essential for all living organisms; however, excessive protein intake can have adverse effects, such as hyperammonemia. Although mechanisms responding to deficiency are well-studied, there a significant gap in our understanding of how organisms adaptively suppress intake. In the present study, utilizing fruit fly, Drosophila melanogaster, we discover that peptide hormone CCHamide1 (CCHa1), secreted by enteroendocrine cells response high-protein diet (HPD), vital suppressing overconsumption protein. Gut-derived CCHa1 received small subset enteric neurons produce short neuropeptide F, thereby modulating protein-specific satiety. Importantly, impairment CCHa1-mediated gut-enteric neuronal axis results ammonia accumulation and shortened lifespan under HPD conditions. Collectively, findings unravel crosstalk gut pathways orchestrate physiological responses prevent adapt dietary overload.

Language: Английский

Citations

4
Adipokine and fat body in flies: Connecting organs DOI Creative Commons
Eleonora Meschi, Rénald Delanoue

Molecular and Cellular Endocrinology, Journal Year: 2021, Volume and Issue: 533, P. 111339 - 111339

Published: June 1, 2021

Language: Английский

Citations

27
Drosophila melanogaster: A Powerful Tiny Animal Model for the Study of Metabolic Hepatic Diseases DOI Creative Commons
Karen C. M. Moraes, Jacques Montagne

Frontiers in Physiology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 16, 2021

Animal experimentation is limited by unethical procedures, time-consuming protocols, and high cost. Thus, the development of innovative approaches for disease treatment based on alternative models in a fast, safe, economic manner an important, yet challenging goal. In this paradigm, fruit-fly Drosophila melanogaster has become powerful model biomedical research, considering its short life cycle low-cost maintenance. addition, biological processes are conserved homologs ∼75% human disease-related genes found fruit-fly. Therefore, been used to evaluate validate functional activities candidate molecules identified via vitro large-scale analyses, as putative agents treat or reverse pathological conditions. context, offers investigate molecular aspects liver diseases, since no effective therapies available those pathologies. Non-alcoholic fatty most common form chronic hepatic dysfunctions, which may progress hepatitis ultimately cirrhosis, thereby increasing risk hepatocellular carcinoma (HCC). This deleterious situation reinforces use accelerate research aimed at deciphering mechanisms that sustain disease. review, we illustrate relevance using address pathologies contribute area.

Language: Английский

Citations

25
Circulating fructose regulates a germline stem cell increase via gustatory receptor–mediated gut hormone secretion in mated Drosophila DOI Creative Commons
Ryo Hoshino, Hiroko Sano, Yuto Yoshinari

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(8)

Published: Feb. 24, 2023

Oogenesis is influenced by multiple environmental factors. In the fruit fly, Drosophila melanogaster, nutrition and mating have large impacts on an increase in female germline stem cells (GSCs). However, it unclear whether these two factors affect this GSC interdependently. Here, we report that dietary sugars are crucial for after mating. Dietary glucose required mating-induced release of neuropeptide F (NPF) from enteroendocrine (EECs), followed NPF-mediated enhancement niche signaling. Unexpectedly, does not directly act NPF-positive EECs. Rather, contributes to elevation hemolymph fructose generated through polyol pathway. Elevated stimulates fructose-specific gustatory receptor, Gr43a, EECs, leading NPF secretion. This study demonstrates circulating fructose, derived sugars, a prerequisite leads egg production

Language: Английский

Citations

11
Nutrient status alters developmental fates via a switch in mitochondrial homeodynamics DOI Creative Commons
Jie Zhang, Suning Liu, Li Yang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 1, 2025

Steroid hormones are powerful endocrine regulators, but little is known about how environmental conditions modulate steroidogenesis to reprogram developmental fates. Here, we use the Drosophila prothoracic gland (PG) investigate a nutrient restriction checkpoint (NRC) ensures or blocks progression and sexual maturation via regulating steroidogenesis. Extensive transcriptome analysis of PG reveals that pre-NRC starvation significantly downregulates mitochondria-associated genes. Pre-NRC reduces prothoracicotropic neuropeptide hormone signaling, insulin TORC1 activity in cells, which prevent mitochondrial fragmentation import Disembodied, key steroidogenic enzyme. Ultimately, causes severe mitophagy proteasome dysfunction, blocking metamorphosis. By contrast, post-NRC does not impair homeostasis cells sit expression induces moderate autophagy promote steroidogenesis, leading precocious This study constitutes paradigm for exploring steroid levels controlled response stress during checkpoints. The principal Drosophila. Here Zhang et al. perform transcriptomic show prior alters production.

Language: Английский

Citations

0
Automated survival monitoring system: exploring starvation resistance in newly hatched larvae DOI Creative Commons

Hiroto Ohki,

Ki‐Hyeon Seong, Takahiro Suzuki

et al.

Applied Entomology and Zoology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Language: Английский

Citations

0