Organelle communication in neurons

A peptidergic neuron in the CNS of a Drosophila pupa. Organelles in green and magenta, peptide in blue. Airyscan confocal image

Organelles are membrane-delimited compartments of a cell that allow for the spatial separation of specialized processes. For example, the lysosome, also referred to as the cell’s stomach, has a low luminal pH optimal for its hydrolases that break down cellular material. Another example is the peroxisomal lumen where hydrogen peroxide is formed during its metabolic processes, which would be toxic to the cell at elevated concentrations, and which are scavenged inside the peroxisome by specialized enzymes. Organelles can engage in heterotypic interactions, when they come into close apposition that is mediated by tether proteins at membrane contact sites.

Neurons are highly specialized and polarized cells, and their somatodendritic and axonal compartments require unique organelle functions and specialized interactions. Organelles engage in dynamic and direct membrane contacts that serve various purposes: exchange of signaling molecules and nutrients, regulation of morphology and neuronal activity, and modulation of the cell’s metabolism.

The Bülow lab seeks to understand how organelle interplay shapes neuronal function and, vice versa, how peripheral cues affect neuronal organelle interplay. We found that phospholipid exchange between ER and mitochondria in dopaminergic neurons triggers the formation of mitochondrial H2O2, a process that is required for neuronal activity (Paradis et al., 2022). In peptidergic neurons, we found that peroxisome – Golgi interaction enables the nutrient-dependent release of neuropeptides (König et al., 2025).

Our favourite model is Drosophila melanogaster, which gives us the opportunity to study organelle dynamics in vivo and in the neuron’s native context, the brain. Moreover, Drosophila with its functionally homologous, specialized organs allows for the investigation of inter-organ effects (Carrera et al., 2024), of dietary effects on organelle communication (König et al., 2025; Sellin et al., 2018) and on systemic effects of neuron function (Paradis et al., 2022).

One type of neurons Darla is particularly interested in are those that express pigment -dispersing factor (pdf), a neuropeptide involved in circadian rhythm. A specific set of pdf-expressing neurons is located in the ventral nerve cord (VNC) of the fly. These neurons are especially helpful for imaging because they are large, well-positioned, and easily identifiable at the tip of the nervous system. 

In the images, you can see a front view of the pdf neurons in the VNC (right) and a lateral view (left), highlighting their distinct morphology. Peroxisomes and mitochondria are labelled with fluorescent markers, and the pdf peptide is labelled with an antibody.

Image credit: Darla Dancourt