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 shortage induces a lipolytic program that leads to the depletion of storage fat and accumulation of free fatty acids (FFA). FFA exert lipotoxic effects on mitochondria and disturb the secretion of neuropeptides such as insulin-like peptides. This alters neuron physiology and systemic metabolism of Pex19 mutants.
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.