Drosophila as a Model System to Study Metabolism

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 4919

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Guest Editor
Division of Science, Pennsylvania State University, Berks Campus, Reading, PA 19610, USA
Interests: Drosophila; lipid metabolism; carbohydrate metabolism; mRNA splicing; insulin
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Special Issue Information

Dear Colleagues,

Defects in cellular and organismal metabolism can result in a number of diseases including obesity and type 2 diabetes, which are very prevalent worldwide. Increasing our knowledge of how metabolism is controlled is essential to better understand the pathogenesis of these diseases; however, studying metabolism in humans is very challenging. An organism that has recently emerged as a model system to study metabolism is the fruit fly, Drosophila melanogaster. Drosophila is an excellent system in which to study metabolism due to its short generation time and lifespan and the high similarity of its genes, cellular and biochemical pathways, and cellular and organ physiology with mammals. In addition, there are many genetic tools available in Drosophila that allow each gene in the genome to be manipulated. With this Special Issue, we aim to bring together a wide range of Drosophila researchers studying many diverse aspects of metabolism in the hope of highlighting the many important discoveries that can be made with flies; this research can ultimately be used to gain a more thorough understanding of metabolic biology in a wide range of biological systems.

Dr. Justin R. DiAngelo
Guest Editor

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Keywords

  • carbohydrate
  • lipid
  • amino acid
  • Drosophila
  • metabolism
  • insulin
  • TOR
  • autophagy
  • fasting

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Published Papers (5 papers)

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Research

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18 pages, 12199 KiB  
Article
Impairment of Muscle Function Causes Pupal Lethality in Flies Expressing the Mitochondrial Alternative Oxidase
by Carlos A. Couto-Lima, Sina Saari, Geovana S. Garcia, Gabriel H. Rocha, Johanna ten Hoeve, Eric Dufour and Marcos T. Oliveira
Biomolecules 2025, 15(4), 570; https://doi.org/10.3390/biom15040570 - 11 Apr 2025
Viewed by 241
Abstract
The mitochondrial alternative oxidase (AOX) from the tunicate Ciona intestinalis has been explored as a potential therapeutic enzyme for human mitochondrial diseases, yet its systemic effects remain poorly understood. Here, we investigate the metabolic and physiological consequences of AOX expression during the development [...] Read more.
The mitochondrial alternative oxidase (AOX) from the tunicate Ciona intestinalis has been explored as a potential therapeutic enzyme for human mitochondrial diseases, yet its systemic effects remain poorly understood. Here, we investigate the metabolic and physiological consequences of AOX expression during the development of Drosophila cultured under dietary stress. We show that the combination of strong, ubiquitous AOX expression and a low-nutrient condition leads to pupal lethality and severe defects in larval musculature, characterized by actin aggregation and muscle shortening. These structural abnormalities correlate with a decrease in larval biomass and motility. Interestingly, the muscle defects and the motility impairments vary in severity among individuals, predicting survival rates at the pupal stage. AOX expression in specific tissues (muscle, nervous system or fat body) does not individually recapitulate the lethal phenotype observed with ubiquitous expressions of the enzyme, indicating a complex metabolic imbalance. Metabolomic analysis revealed that the low-nutrient diet and AOX expression have opposite effects on most metabolites analyzed, especially in the levels of amino acids. Notably, supplementation of the low-nutrient diet with the essential amino acids methionine and/or tryptophan partially rescues pupal viability, body size, muscle morphology, and locomotion, whereas supplementation with proline and/or glutamate does not, highlighting a specific perturbation in amino acid metabolism rather than general bioenergetic depletion. These findings demonstrate that AOX expression disrupts metabolic homeostasis, with developmental and physiological consequences that must be considered when evaluating AOX for therapeutic applications. Full article
(This article belongs to the Special Issue Drosophila as a Model System to Study Metabolism)
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15 pages, 2436 KiB  
Article
Adipocyte-Derived CCHamide-1, Eiger, Growth-Blocking Peptide 3, and Unpaired 2 Regulate Drosophila melanogaster Oogenesis
by Chad Simmons, Isaiah H. Williams, Tancia W. Bradshaw and Alissa Richmond Armstrong
Biomolecules 2025, 15(4), 513; https://doi.org/10.3390/biom15040513 - 1 Apr 2025
Viewed by 370
Abstract
In addition to energy storage, adipose tissue communication to other organs plays a key role in regulating organismal physiology. While the link between adipose tissue dysfunction and pathophysiology, including diabetes, chronic inflammation, and infertility, is clear, the molecular mechanisms that underlie these associations [...] Read more.
In addition to energy storage, adipose tissue communication to other organs plays a key role in regulating organismal physiology. While the link between adipose tissue dysfunction and pathophysiology, including diabetes, chronic inflammation, and infertility, is clear, the molecular mechanisms that underlie these associations have not been fully described. We use Drosophila melanogaster as a model to better understand how adipose tissue communicates to the ovary. In this study, we utilized D. melanogaster’s robust genetic toolkit to examine the role of five adipokines known to control larval growth during development, CCHamide-1, CCHamide-2, eiger, Growth-blocking peptide 3, and unpaired 2 in regulating oogenesis. We show that the adult fat body expresses these “larval” adipokines. Our data indicate that ovarian germline stem cell maintenance does not require these adipokines. However, adipocyte-derived CCHamide-1, eiger, Growth-blocking peptide 3, and unpaired 2 influence early and late germline survival as well as ovulation. Thus, this work uncovers several adipokines that mediate fat-to-ovary communication. Full article
(This article belongs to the Special Issue Drosophila as a Model System to Study Metabolism)
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18 pages, 7926 KiB  
Article
EMC1 Is Required for the Sarcoplasmic Reticulum and Mitochondrial Functions in the Drosophila Muscle
by Carlos Antonio Couto-Lima, Maiaro Cabral Rosa Machado, Lucas Anhezini, Marcos Túlio Oliveira, Roberto Augusto da Silva Molina, Rodrigo Ribeiro da Silva, Gabriel Sarti Lopes, Vitor Trinca, David Fernando Colón, Pablo M. Peixoto, Nadia Monesi, Luciane Carla Alberici, Ricardo Guelerman P. Ramos and Enilza Maria Espreafico
Biomolecules 2024, 14(10), 1258; https://doi.org/10.3390/biom14101258 - 5 Oct 2024
Cited by 1 | Viewed by 1737
Abstract
EMC1 is part of the endoplasmic reticulum (ER) membrane protein complex, whose functions include the insertion of transmembrane proteins into the ER membrane, ER–mitochondria contact, and lipid exchange. Here, we show that the Drosophila melanogaster EMC1 gene is expressed in the somatic musculature and [...] Read more.
EMC1 is part of the endoplasmic reticulum (ER) membrane protein complex, whose functions include the insertion of transmembrane proteins into the ER membrane, ER–mitochondria contact, and lipid exchange. Here, we show that the Drosophila melanogaster EMC1 gene is expressed in the somatic musculature and the protein localizes to the sarcoplasmic reticulum (SR) network. Muscle-specific EMC1 RNAi led to severe motility defects and partial late pupae/early adulthood lethality, phenotypes that are rescued by co-expression with an EMC1 transgene. Motility impairment in EMC1-depleted flies was associated with aberrations in muscle morphology in embryos, larvae, and adults, including tortuous and misaligned fibers with reduced size and weakness. They were also associated with an altered SR network, cytosolic calcium overload, and mitochondrial dysfunction and dysmorphology that impaired membrane potential and oxidative phosphorylation capacity. Genes coding for ER stress sensors, mitochondrial biogenesis/dynamics, and other EMC components showed altered expression and were mostly rescued by the EMC1 transgene expression. In conclusion, EMC1 is required for the SR network’s mitochondrial integrity and influences underlying programs involved in the regulation of muscle mass and shape. We believe our data can contribute to the biology of human diseases caused by EMC1 mutations. Full article
(This article belongs to the Special Issue Drosophila as a Model System to Study Metabolism)
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11 pages, 1819 KiB  
Article
Glut1 Functions in Insulin-Producing Neurons to Regulate Lipid and Carbohydrate Storage in Drosophila
by Matthew R. Kauffman and Justin R. DiAngelo
Biomolecules 2024, 14(8), 1037; https://doi.org/10.3390/biom14081037 - 20 Aug 2024
Cited by 1 | Viewed by 1773
Abstract
Obesity remains one of the largest health problems in the world, arising from the excess storage of triglycerides (TAGs). However, the full complement of genes that are important for regulating TAG storage is not known. The Glut1 gene encodes a Drosophila glucose transporter [...] Read more.
Obesity remains one of the largest health problems in the world, arising from the excess storage of triglycerides (TAGs). However, the full complement of genes that are important for regulating TAG storage is not known. The Glut1 gene encodes a Drosophila glucose transporter that has been identified as a potential obesity gene through genetic screening. Yet, the tissue-specific metabolic functions of Glut1 are not fully understood. Here, we characterized the role of Glut1 in the fly brain by decreasing neuronal Glut1 levels with RNAi and measuring glycogen and TAGs. Glut1RNAi flies had decreased TAG and glycogen levels, suggesting a nonautonomous role of Glut1 in the fly brain to regulate nutrient storage. A group of hormones that regulate metabolism and are expressed in the fly brain are Drosophila insulin-like peptides (Ilps) 2, 3, and 5. Interestingly, we observed blunted Ilp3 and Ilp5 expression in neuronal Glut1RNAi flies, suggesting Glut1 functions in insulin-producing neurons (IPCs) to regulate whole-organism TAG and glycogen storage. Consistent with this hypothesis, we also saw fewer TAGs and glycogens and decreased expression of Ilp3 and Ilp5 in flies with IPC-specific Glut1RNAi. Together, these data suggest Glut1 functions as a nutrient sensor in IPCs, controlling TAG and glycogen storage and regulating systemic energy homeostasis. Full article
(This article belongs to the Special Issue Drosophila as a Model System to Study Metabolism)
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Review

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13 pages, 551 KiB  
Review
Drosophila as a Genetic Model System to Study Organismal Energy Metabolism
by Arely V. Diaz, Izel Tekin and Tânia Reis
Biomolecules 2025, 15(5), 652; https://doi.org/10.3390/biom15050652 (registering DOI) - 1 May 2025
Abstract
Metabolism is the essential process by which an organism converts nutrients into energy to fuel growth, development, and repair. Metabolism at the level of a multicellular, multi-organ animal is inherently more complex than metabolism at the single-cell level. Indeed, each organ also must [...] Read more.
Metabolism is the essential process by which an organism converts nutrients into energy to fuel growth, development, and repair. Metabolism at the level of a multicellular, multi-organ animal is inherently more complex than metabolism at the single-cell level. Indeed, each organ also must maintain its own homeostasis to function. At all three scales, homeostasis is a defining feature: as energy sources and energetic demands wax and wane, the system must be robust. While disruption of organismal energy homeostasis can be manifested in different ways in humans, obesity (defined as excess body fat) is an increasingly common outcome of metabolic imbalance. Here we will discuss the genetic basis of metabolic dysfunction that underlies obesity. We focus on what we are learning from Drosophila melanogaster as a model organism to explore and dissect genetic causes of metabolic dysfunction in the context of a whole organism. Full article
(This article belongs to the Special Issue Drosophila as a Model System to Study Metabolism)
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