PT  - JOURNAL ARTICLE
AU  - Sreejith, Perinthottathil
AU  - Lolo, Sara
AU  - Patten, Kristen R.
AU  - Gunasinghe, Maduka
AU  - More, Neya
AU  - Pallanck, Leo J.
AU  - Bharadwaj, Rajnish
TI  - Nazo, the <em>Drosophila</em> homolog of the NBIA-mutated protein – c19orf12, is required for triglyceride homeostasis
AID  - 10.1101/2022.09.29.510106
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.09.29.510106
4099  - http://biorxiv.org/content/early/2022/09/30/2022.09.29.510106.short
4100  - http://biorxiv.org/content/early/2022/09/30/2022.09.29.510106.full
AB  - Lipid dyshomeostasis has been implicated in a variety of diseases ranging from obesity to neurodegenerative disorders such as NBIA. Here, we uncover the physiological role of Nazo, the Drosophila homolog of the NBIA-mutated protein – c19orf12, whose function has been elusive. Ablation of Drosophila c19orf12 homologs leads to dysregulation of multiple lipid metabolism genes. nazo mutants exhibit markedly reduced gut lipid droplet and whole-body triglyceride contents. Consequently, they are sensitive to starvation and oxidative stress. Nazo localizes to ER-lipid droplet contact sites and is required for maintaining normal levels of Perilipin2, an inhibitor of the lipase – Brummer. Concurrent knockdown of Brummer or overexpression of Perilipin2 rescues the nazo phenotype, suggesting that this defect may arise from diminished Perilipin2 on lipid droplets leading to aberrant Brummer-mediated lipolysis. Our findings provide novel insights into the role of c19orf12 as a possible link between lipid dyshomeostasis and neurodegeneration, particularly in the context of NBIA.Competing Interest StatementThe authors have declared no competing interest.