Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila
Summary: Maintaining metabolic homeostasis requires coordinated nutrient utilization between intracellular organelles and across multiple organ systems. Many organs rely heavily on mitochondria to generate (ATP) from glucose, or stored glycogen. Proteins required for ATP generation are encoded in bo...
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Elsevier
2025-01-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224028384 |
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| author | Heidi Bretscher Michael B. O’Connor |
| author_facet | Heidi Bretscher Michael B. O’Connor |
| author_sort | Heidi Bretscher |
| collection | DOAJ |
| description | Summary: Maintaining metabolic homeostasis requires coordinated nutrient utilization between intracellular organelles and across multiple organ systems. Many organs rely heavily on mitochondria to generate (ATP) from glucose, or stored glycogen. Proteins required for ATP generation are encoded in both nuclear and mitochondrial DNA (mtDNA). We show that motoneuron to muscle signaling by the TGFβ/Activin family member Actβ positively regulates glycogen levels during Drosophila development. Remarkably, we find that levels of stored glycogen are unaffected by altering cytoplasmic glucose catabolism. Instead, loss of Actβ reduces levels of nuclearly encoded genes required for mtDNA replication, transcription, and translation and mtDNA levels. Direct RNAi knockdown of nuclearly encoded mtDNA expression factors in muscle also results in decreased glycogen stores. Lastly, expressing an activated form of the type I receptor Baboon in muscle restores both glycogen and mtDNA levels in actβ mutants, thereby confirming a direct link between Actβ signaling, glycogen homeostasis, and mtDNA expression factors. |
| format | Article |
| id | doaj-art-612ad0bc7f3d48b68a774869a56060ba |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-612ad0bc7f3d48b68a774869a56060ba2025-01-04T04:56:48ZengElsevieriScience2589-00422025-01-01281111611Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in DrosophilaHeidi Bretscher0Michael B. O’Connor1Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USADepartment of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA; Corresponding authorSummary: Maintaining metabolic homeostasis requires coordinated nutrient utilization between intracellular organelles and across multiple organ systems. Many organs rely heavily on mitochondria to generate (ATP) from glucose, or stored glycogen. Proteins required for ATP generation are encoded in both nuclear and mitochondrial DNA (mtDNA). We show that motoneuron to muscle signaling by the TGFβ/Activin family member Actβ positively regulates glycogen levels during Drosophila development. Remarkably, we find that levels of stored glycogen are unaffected by altering cytoplasmic glucose catabolism. Instead, loss of Actβ reduces levels of nuclearly encoded genes required for mtDNA replication, transcription, and translation and mtDNA levels. Direct RNAi knockdown of nuclearly encoded mtDNA expression factors in muscle also results in decreased glycogen stores. Lastly, expressing an activated form of the type I receptor Baboon in muscle restores both glycogen and mtDNA levels in actβ mutants, thereby confirming a direct link between Actβ signaling, glycogen homeostasis, and mtDNA expression factors.http://www.sciencedirect.com/science/article/pii/S2589004224028384Molecular biologyCell biology |
| spellingShingle | Heidi Bretscher Michael B. O’Connor Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila iScience Molecular biology Cell biology |
| title | Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila |
| title_full | Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila |
| title_fullStr | Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila |
| title_full_unstemmed | Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila |
| title_short | Glycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila |
| title_sort | glycogen homeostasis and mitochondrial dna expression require motor neuron to muscle tgf β activin signaling in drosophila |
| topic | Molecular biology Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224028384 |
| work_keys_str_mv | AT heidibretscher glycogenhomeostasisandmitochondrialdnaexpressionrequiremotorneurontomuscletgfbactivinsignalingindrosophila AT michaelboconnor glycogenhomeostasisandmitochondrialdnaexpressionrequiremotorneurontomuscletgfbactivinsignalingindrosophila |