5.9
CiteScore
5.9
Impact Factor

2019 Vol. 46, No. 4

Editorial
Understanding human diseases using Drosophila
Jun-Yuan Ji, Chun Han, Wu-Min Deng
2019, 46(4): 155-156. doi: 10.1016/j.jgg.2019.04.001
Abstract (94) HTML PDF (4)
Abstract:
Review
Understanding the importance of autophagy in human diseases using Drosophila
Arindam Bhattacharjee, Áron Szabó, Tamás Csizmadia, Hajnalka Laczkó-Dobos, Gábor Juhász
2019, 46(4): 157-169. doi: 10.1016/j.jgg.2019.03.007
Abstract (134) HTML PDF (6)
Abstract:
Autophagy is a lysosome-dependent intracellular degradation pathway that has been implicated in the pathogenesis of various human diseases, either positively or negatively impacting disease outcomes depending on the specific context. The majority of medical conditions including cancer, neurodegenerative diseases, infections and immune system disorders and inflammatory bowel disease could probably benefit from therapeutic modulation of the autophagy machinery. Drosophila represents an excellent model animal to study disease mechanisms thanks to its sophisticated genetic toolkit, and the conservation of human disease genes and autophagic processes. Here, we provide an overview of the various autophagy pathways observed both in flies and human cells (macroautophagy, microautophagy and chaperone-mediated autophagy), and discuss Drosophila models of the above-mentioned diseases where fly research has already helped to understand how defects in autophagy genes and pathways contribute to the relevant pathomechanisms.
Organelle aging: Lessons from model organisms
Mark Bouska, Kerui Huang, Ping Kang, Hua Bai
2019, 46(4): 171-185. doi: 10.1016/j.jgg.2019.03.011
Abstract (104) HTML PDF (4)
Abstract:
Most cellular processes descend into failure during aging. While a large collection of longevity pathways has been identified in the past decades, the mechanism for age-related decline of cellular homeostasis and organelle function remains largely unsolved. It is known that many organelles undergo structural and functional changes during normal aging, which significantly contributes to the decline of tissue function at old ages. Since recent studies have revealed an emerging role of organelles as regulatory hubs in maintaining cellular homeostasis, understanding of organelle aging will provide important insights into the cellular basis of organismal aging. Here we review current progress on the characterization of age-dependent structural and functional alterations in the more well-studied organelles, as well as the known mechanisms governing organelle aging in model organisms, with a special focus on the fruit fly Drosophila melanogaster.
Die in pieces: How Drosophila sheds light on neurite degeneration and clearance
Maria L. Sapar, Chun Han
2019, 46(4): 187-199. doi: 10.1016/j.jgg.2019.03.010
Abstract (128) HTML PDF (3)
Abstract:
Dendrites and axons are delicate neuronal membrane extensions that undergo degeneration after physical injuries. In neurodegenerative diseases, they often degenerate prior to neuronal death. Understanding the mechanisms of neurite degeneration has been an intense focus of neurobiology research in the last two decades. As a result, many discoveries have been made in the molecular pathways that lead to neurite degeneration and the cell-cell interactions responsible for the subsequent clearance of neuronal debris. Drosophila melanogaster has served as a prime in vivo model system for identifying and characterizing the key molecular players in neurite degeneration, thanks to its genetic tractability and easy access to its nervous system. The knowledge learned in the fly provided targets and fuel for studies in other model systems that have further enhanced our understanding of neurodegeneration. In this review, we will introduce the experimental systems developed in Drosophila to investigate injury-induced neurite degeneration, and then discuss the biological pathways that drive degeneration. We will also cover what is known about the mechanisms of how phagocytes recognize and clear degenerating neurites, and how recent findings in this area enhance our understanding of neurodegenerative disease pathology.
Human mitochondrial DNA diseases and Drosophila models
Zhe Chen, Fan Zhang, Hong Xu
2019, 46(4): 201-212. doi: 10.1016/j.jgg.2019.03.009
Abstract (147) HTML PDF (5)
Abstract:
Mutations that disrupt the mitochondrial genome cause a number of human diseases whose phenotypic presentation varies widely among tissues and individuals. This variability owes in part to the unconventional genetics of mitochondrial DNA (mtDNA), which includes polyploidy, maternal inheritance and dependence on nuclear-encoded factors. The recent development of genetic tools for manipulating mitochondrial genome in Drosophila melanogaster renders this powerful model organism an attractive alternative to mammalian systems for understanding mtDNA-related diseases. In this review, we summarize mtDNA genetics and human mtDNA-related diseases. We highlight existing Drosophila models of mtDNA mutations and discuss their potential use in advancing our knowledge of mitochondrial biology and in modeling human mitochondrial disorders. We also discuss the potential and present challenges of gene therapy for the future treatment of mtDNA diseases.
Perspectives on gene expression regulation techniques in Drosophila
Rong-Gang Xu, Xia Wang, Da Shen, Jin Sun, Huan-Huan Qiao, Fang Wang, Lu-Ping Liu, Jian-Quan Ni
2019, 46(4): 213-220. doi: 10.1016/j.jgg.2019.03.006
Abstract (108) HTML PDF (4)
Abstract:
Gene expression regulation, including loss-of-function and gain-of-function assays, is a powerful method to study developmental and disease mechanisms. Drosophila melanogaster is an ideal model system particularly well-equipped with many genetic tools. In this review, we describe and discuss the gene expression regulation techniques recently developed and their applications, including the CRISPR/Cas9-triggered heritable mutation system, CRISPR/dCas9-based transcriptional activation (CRISPRa) system, and CRISPR/dCas9-based transcriptional repression (CRISPRi) system, as well as the next-generation transgenic RNAi system. The main purpose of this review is to provide the fly research community with an updated summary of newly developed gene expression regulation techniques and help the community to select appropriate methods and optimize the research strategy.
Original research
HDAC6 regulates lipid droplet turnover in response to nutrient deprivation via p62-mediated selective autophagy
Yan Yan, Hao Wang, Chuanxian Wei, Yuanhang Xiang, Xuehong Liang, Chung-Weng Phang, Renjie Jiao
2019, 46(4): 221-229. doi: 10.1016/j.jgg.2019.03.008
Abstract (118) HTML PDF (7)
Abstract:
Autophagy has been evolved as one of the adaptive cellular processes in response to stresses such as nutrient deprivation. Various cellular cargos such as damaged organelles and protein aggregates can be selectively degraded through autophagy. Recently, the lipid storage organelle, lipid droplet (LD), has been reported to be the cargo of starvation-induced autophagy. However, it remains largely unknown how the autophagy machinery recognizes the LDs and whether it can selectively degrade LDs. In this study, we show that Drosophila histone deacetylase 6 (dHDAC6), a key regulator of selective autophagy, is required for the LD turnover in the hepatocyte-like oenocytes in response to starvation. HDAC6 regulates LD turnover via p62/SQSTM1 (sequestosome 1)-mediated aggresome formation, suggesting that the selective autophagy machinery is required for LD recognition and degradation. Furthermore, our results show that the loss of dHDAC6 causes steatosis in response to starvation. Our findings suggest that there is a potential link between selective autophagy and susceptible predisposition to lipid metabolism associated diseases in stress conditions.
Letter to the editor
Lipid storage regulator CdsA is essential for Drosophila metamorphosis
Yuan Liu, Yuan Ji, Xia Li, Guanghou Shui, Xun Huang
2019, 46(4): 231-234. doi: 10.1016/j.jgg.2019.02.008
Abstract (111) HTML PDF (8)
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