Organelle communication in neuron function and physiology

Organelles form dynamic contacts with each other to exchange material and signaling cues. An important type of organelle communication exists between mitochondria and peroxisomes. Peroxisomes assist mitochondria in fatty acid oxidation (FAO) and use the same machinery for fission. We found that Drosophila mutants for the peroxisome biogenesis factor Pex19 deregulate mitochondrial FAO, which results in depletion of medium-chain fatty acids. This fatty acid shift has major implications for neuron physiology. My lab is currently exploring the roles of peroxisomal membrane contacts, peroxisome metabolism and of Pex19 in the secretion of neuropeptides: we show that Pex19 is required for the nutrient-dependent release of insulin-like peptides from peptidergic neurons in Drosophila.

Contacts between the endoplasmic reticulum (ER), mitochondria and peroxisomes regulate the redox status of a cell. Pex19 interacts with the ER protein Creld, and loss of Creld function impairs peroxisome biogenesis in neurons. We found that Creld is required for the formation of ER-mitochondria contacts in dopaminergic neurons. In response to low respiratory complex I activity, ER-mitochondria contacts promote phospholipid flux, which supports complex I function. In Creld mutants, constant complex I inactivity reduces H2O2 formation in dopaminergic neurons and impairs their activity. Our studies show the impact of organelle communication on neuron function.