Dysfunction of lipid storage droplet-2 suppresses endoreplication and induces JNK pathway-mediated apoptotic cell death in Drosophila salivary glands

Abstract

The lipid storage droplet-2 (LSD-2) protein of Drosophila is a homolog of mammalian perilipin 2, which is essential for promoting lipid accumulation and lipid droplet formation. The function of LSD-2 as a regulator of lipolysis has also been demonstrated. However, other LSD-2 functions remain unclear. To investigate the role of LSD-2, we performed tissue-specific depletion in the salivary glands of Drosophila using a combination of the Gal4-upstream activating sequence system and RNA interference. LSD-2 depletion inhibited the entry of salivary gland cells into the endoreplication cycle and delayed this process by enhancing CycE expression, disrupting the development of this organ. The deficiency of LSD-2 expression enhanced reactive oxygen species production in the salivary gland and promoted JNK-dependent apoptosis by suppressing dMyc expression. This phenomenon did not result from lipolysis. Therefore, LSD-2 is vital for endoreplication cell cycle and cell death programs.

Interplay of EGFR, JNK and ROS signalling in soma-germline communication in theDrosophilatestis

“…ROS can activate JNK and p38 through a positive feedback loop, and thereby regulate the balance between apoptosis and autophagy vs cell competition, immunity, stem cell and tissue regeneration in many tissues and organs across species (Binh et al, 2022; Diwanji and Bergmann, 2020; Kucinski et al, 2017; Santabarbara-Ruiz et al, 2015) [reviewed also in (Herrera et al, 2021; La Marca and Richardson, 2020; Serras, 2022; Sinenko et al, 2021; Sui et al, 2014; Yue and Lopez, 2020; Zhou and Sakurai, 2022)]. Increased levels of ROS can propagate paracrine signals that are sensed by neighbouring healthy cells, which involve activation of Ask1 and subsequent phosphorylation and activation of JNK and p38 (Esteban-Collado et al, 2023; Serras, 2022).…”

Depletion of lipid storage droplet‐1 delays endoreplication progression and induces cell death in Drosophila salivary gland

“…Previous studies have reported that LSD-2 is expressed in lipid droplets of secretory cells in the salivary gland and in the lumen of the tube where duct cells reside (Binh et al, 2022). Moreover, the role of LSD-2 in salivary gland development has been reported (Binh et al, 2022). Bi et al reported that Drosophila perilipin 1/LSD-1 localizes to large lipid droplets within larval fat bodies, whereas perilipin 2/LSD-2 is predominantly found on smaller lipid droplets (Bi et al, 2012).…”

“…We have previously reported the location of LSD-1 in the Drosophila wing disc, which is a non-adipose tissue (Binh et al, 2019) (Men et al, 2016), and that LSD-2 in salivary glands localizes in the lumen of the tube in which the duct cells resided, and in the intracellular lipid droplets of secretory cells (Binh et al, 2022). In this study, LSD-1 in the salivary glands of wandering third-instar larvae of Drosophila was analyzed using Lsd-1-GFP flies which express LSD-1 tagged at the Cterminus with GFP by knocking in the GFP gene (Figure 1b,e).…”

“…We have previously demonstrated that Lsd-2 dysfunction suppresses the endoreplication process resulting in the formation of extremely small salivary glands containing cells with smaller nuclei than wild-type cells (Binh et al, 2022).…”

The Janus-Faced Role of Lipid Droplets in Aging: Insights from the Cellular Perspective

“…Similarly, the fat body of LSD-2 −/− homozygous larva contains less than 75% TAG as seen in normal flies. Pointing to additional functions not directly related to lipid storage, LSD-2 is also required for the endoreplication of cells in the larval salivary gland, with the loss of LSD-2 activity resulting in enhanced ROS generation and stimulation of JNK (c-jun amino-terminal kinase)-dependent apoptotic cell death [ 174 ]. Similarly, LSD-2 provides lipid storage in imaginal discs during metamorphosis, but also plays a distinct role in imaginal disc cell growth and differentiation.…”