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Insulin-like peptide secretion is mediated by peroxisome-Golgi interplay

de Marie A. König, Nicole Kucharowski, Darla P. Dancourt Ramos, Hannah Soyka, Klaus Wunderling, Torsten R. Bülow, Mohamed H. Yaghmour, Christoph Thiele, Jan M. Ache, Lars Kuerschner e Margret H. Bülow

Publicado: 27 de maio de 2025
Servidor: bioRxiv
DOI: 10.1101/2025.05.26.656179

Resumo

Insulin is a peptide hormone that is secreted in Golgi-derived dense-core vesicles from mammalian pancreatic beta-cells in response to nutrients. InDrosophila melanogaster, three insulin-like peptides are secreted as neuropeptides from the insulin-producing cells in the brain. Peroxisomes are lipid-metabolizing organelles that engage into various membrane contact sites with other organelles. Impaired peroxisomal metabolism has been associated with beta-cell apoptosis and impaired insulin secretion. How peroxisomes contribute to insulin and neuropeptide secretion is unknown. Here we demonstrate that peroxisomes interact with the Golgi apparatus inDrosophilainsulin-producing cells. Secretion of insulin-like peptide 2 is cell-intrinsically impaired in mutants lacking the peroxisome assembly factor Pex19. Loss of peroxisomes shifts the profile of sphingolipids towards longer sphingoid bases and leads to accumulation of sphingolipids in the Golgi. We show that peroxisomes dynamically interact with the Golgi in insulin-producing cells and that Pex19 directly contributes to peroxisome-Golgi interaction via the fatty acyl-CoA reductase FAR2/waterproof in the peroxisomal membrane. We propose that this peroxisome-Pex19-Golgi axis is required to adjust Golgi membranes upon starvation by withdrawing lipids with longer side chains, thereby optimizing Golgi membrane flexibility for dense-core vesicle secretion upon refeeding.

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De autoria de Ink Pelican do/a HHMI Transparent and Accountable Peer Review Training Pilot

König et al. explore the relationship between peroxisomes and neuropeptides using the insulin-producing cells (IPCs) in Drosophila melanogaster. By utilizing a very clean assay it is evident that Dilp2 accumulates in some of the IPCs in conditions of starvation and is no longer after feeding. This…

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Avaliações PREreview de Insulin-like peptide secretion is mediated by peroxisome-Golgi interplay

1 Avaliação PREreview