Secretion of neuropeptides relies on Golgi-derived secretory granules. For example, insulin-like peptides (dilps) are secreted in response to nutritional cues from insulin-producing cells (IPCs) in Drosophila. We uncovered a critical, previously unrecognized role for peroxisomes in dilp secretion: peroxisomes engage into functional contacts with the Golgi apparatus in IPCs by interaction of the peroxisomal assembly factor Pex19, the peroxisomal fatty acid reductase FAR2/waterproof and Golgi proteins.

Pex19 mutants lack functional peroxisomes, resulting in disturbed lipid homeostasis, mitochondrial hyperactivity and early lethality (Bülow et al., 2018; Sellin et al., 2018). Here we show that Pex19 mutants cannot secrete dilps upon a nutrient stimulus due to disrupted peroxisome – Golgi interaction. Due to fatty acid imbalance in sphingolipids, these lipids accumulate in Golgi membranes of Pex19 mutants. This compromises Golgi membrane flexibility, hindering dense-core vesicle dynamics and reducing secretion of insulin-like peptide 2 (dilp2).

We propose a model in which during starvation peroxisomes help “strip” long-chain lipids from Golgi membranes via the Pex19–FAR2 axis. This lipid remodeling promotes membrane flexibility needed for vesicle formation and dilp2 secretion upon refeeding. Our work highlights a new function for peroxisome-Golgi contact sites.