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The synaptic cell adhesion molecule, neurexin-1 (NRXN1), has previously been implicated in autism, and here we show that in Drosophila melanogaster, the homologue of NRXN1, called Nrx-1, regulates energy metabolism and nutrient homeostasis. First, we show that Nrx-1-null flies exhibit decreased resistance to nutrient deprivation and heat stress compared to controls. Additionally, Nrx-1 mutants exhibit a significantly altered metabolic profile characterized by decreased lipid and carbohydrate stores. Nrx-1-null Drosophila also exhibit diminished levels of nicotinamide adenine dinucleotide (NAD+), an important coenzyme in major energy metabolism pathways. Moreover, loss of Nrx-1 resulted in striking abnormalities in mitochondrial morphology in the flight muscle of Nrx-1-null Drosophila and impaired flight ability in these flies. Further, following a mechanical shock Nrx-1-null flies exhibited seizure-like activity, a phenotype previously linked to defects in mitochondrial metabolism and a common symptom of patients with NRXN1 deletions. The current studies indicate a novel role for NRXN1 in the regulation of energy metabolism and uncover a clinically relevant seizure phenotype in Drosophila lacking Nrx-1.<\/jats:p>","DOI":"10.1093\/hmg\/ddac115","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T17:12:14Z","timestamp":1653585134000},"page":"3422-3438","source":"Crossref","is-referenced-by-count":11,"title":["Loss of<i>neurexin-1<\/i>in<i>Drosophila melanogaster<\/i>results in altered energy metabolism and increased seizure susceptibility"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0097-437X","authenticated-orcid":false,"given":"Kyra A","family":"Levy","sequence":"first","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Neuroscience Graduate Group, University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Autism Spectrum Program of Excellence, University of Pennsylvania , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana D","family":"Weisz","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Autism Spectrum Program of Excellence, University of Pennsylvania , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Jongens","sequence":"additional","affiliation":[{"name":"Department of Genetics, Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 , USA"},{"name":"Autism Spectrum Program of Excellence, University of Pennsylvania , Philadelphia, PA 19104 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"2022101308081094500_ref1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1002\/mrdd.20023","article-title":"Sleep disorders, epilepsy, and autism","volume":"10","author":"Malow","year":"2004","journal-title":"Ment. 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