| Summary: | The presenilin-associated rhomboid-like (<i>PARL</i>) gene was found to contribute to mitochondrial morphology and function and was linked to familial Parkinson’s disease (PD). The <i>PARL</i> gene product is a mitochondrial intramembrane cleaving protease that acts on a number of mitochondrial proteins involved in mitochondrial morphology, apoptosis, and mitophagy. To date, functional and genetic studies of <i>PARL</i> have been mainly performed in mammals. However, little is known about <i>PARL</i> function and its role in dopaminergic (DA) neuron development in vertebrates. The zebrafish genome comprises two <i>PARL</i> paralogs: <i>parla</i> and <i>parlb</i>. Here, we established a loss-of-function mutation in <i>parla</i> via CRISPR/Cas9-mediated mutagenesis. We examined DA neuron numbers in the adult brain and expression of genes associated with DA neuron function in larvae and adults. We show that loss of <i>parla</i> function results in loss of DA neurons, mainly in the olfactory bulb. Changes in the levels of <i>tyrosine hydroxylase</i> transcripts supported this neuronal loss. Expression of <i>fis1</i>, a gene involved in mitochondrial fission, was increased in <i>parla</i> mutants. Finally, we showed that loss of <i>parla</i> function translates into impaired olfaction and altered locomotion parameters. These results suggest a role for <i>parla</i> in the development and/or maintenance of DA neuron function in zebrafish.
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