Research - Institute of Genetics - Developmental Genetics Unit - Momentum Drosophila Autophagy Research Group

scientific adviser

Gábor HORVÁTH senior research associate
Arindam BHATTACHARJEE research associate
Hajnalka HEVÉRNÉ LACZKÓ-DOBOS research associate
Tamás MARUZS research associate
Áron SZABÓ research associate
Viktória KISS scientific administrator
Dalma BÖRCSÖK Ph.D. student
András JIPA Ph.D. student
Adél ÜRMÖSI Ph.D. student
Hussein ABUAMMAR Ph.D. student
Poulami BANIK ITC student
Asha Kiran MADDALI ITC student
Szilvia BOZSÓ laboratory assistant


Autophagy is a process of intracellular self-digestion in lysosomes. During the main pathway, a phagophore membrane cistern engulfs portions of the cytoplasm to form a double-membrane autophagosome. This transport vesicle then fuses with a lysosome (or endosome) to give rise to an autolysosome (or amphisome). Finally, the building blocks generated by degradation of cargo are recycled in synthetic reactions or energy production. Autophagy is usually enhanced by adverse conditions, such as starvation or downregulation of cellular growth signaling, to ensure survival of cells and organisms.

Evolutionarily conserved core Atg genes required for autophagosome formation were discovered in the mid-1990s in yeast. Knowing a set of gene products involved in autophagy made it possible to carry out functional studies of autophagy in higher eukaryotes, and also provided simple assays to monitor this process, for example by following fluorescently tagged Atg proteins such as Atg8/LC3. These tools led to a revolution of autophagy research, with the number of related publications growing from 80 in 1999 to more than 4300 in 2014. It has become clear by now that misregulation of autophagy is involved in various diseases, including cancer, infections, neurodegeneration, obesity, and aging.

Drosophila is one of the most popular animal models, and we have successfully used it for the functional analysis of autophagy in the past. For example, our Atg7 null mutant flies turned out to be viable but short-lived and stress-sensitive, due to the accumulation of pathological protein aggregates and dysfunctional mitochondria in various tissues and organs including the brain.

Figure 1. Autophagy is induced in response to starvation or during normal development in the liver- and fat tissue-like larval fat body, a polyploidy metabolic and storage organ.

Another main advantage of Drosophila is that it allows the discovery of new genes involved in a given process. We have recently identified numerous gene products that are important for autophagy in a genome-wide RNAi screen carried out in the larval fat body, including the transcription factor Myc that is involved in autophagosome formation, and we have shown that, surprisingly, its overexpression increases both cell growth and autophagy. In addition, we identified Syntaxin 17/Syx17 as the autophagosomal SNARE, which binds to the tethering complex HOPS to promote the fusion of autophagosomes with endosomes and lysosomes. Importantly, Syx17 mutant flies are also viable but short-lived, and exhibit severe neuromuscular dysfunction.

Currently, we search for new factors involved in autophagy using a variety of screening methods including RNAi and proteomics, and we are analyzing the role of Atg genes in various organs including the intestine, ovary and testis.

Figure 2. Clones of cells expressing an RNAi transgene that silences Atg2 expression (marked by GFP expression) are strongly impaired in starvation-induced autophagy, as detected by the lack of Lysotracker Red (or mCherry-Atg8a) positive autolysosomes that are normally formed in neighboring cells.

Selected publications

Nagy P, Kovacs L, Sandor GO, Juhasz G. (2016) Stem cell-specific endocytic degradation defects lead to intestinal dysplasia in Drosophila. Dis Model Mech. 2016 Feb 26.

Takats S, Varga A, Pircs K, Juhasz G. (2015) Loss of Drosophila Vps16A enhances autophagosome formation through reduced Tor activity. Autophagy. 2015;11(8):1209-15.

Nagy P, Varga A, Kovacs AL, Takats S, Juhasz G. (2015) How and why to study autophagy in Drosophila: it's more than just a garbage chute. Methods. 75:151-61.

Takats S, Pircs K, Nagy P, Varga A, Karpati M, Hegedus K, Kramer H, Kovacs AL, Sass M, Juhasz G. (2014) Interaction of the HOPS complex with Syntaxin 17 mediates autophagosome clearance in Drosophila. Mol Biol Cell. 25(8):1338-54.

Nagy P, Karpati M, Varga A, Pircs K, Venkei Z, Takats S, Varga K, Erdi B, Hegedus K, Juhasz G. (2014) Atg17/FIP200 localizes to perilysosomal Ref(2)P aggregates and promotes autophagy by activation of Atg1 in Drosophila. Autophagy. 10(3):453-67.

Nagy P, Varga A, Pircs K, Hegedus K, Juhasz G. (2013) Myc-driven overgrowth requires unfolded protein response-mediated induction of autophagy and antioxidant responses in Drosophila melanogaster. PLoS Genet. 9(8):e1003664

Takats S, Nagy P, Varga A, Pircs K, Karpati M, Varga K, Kovacs AL, Hegedus K, Juhasz G. (2013) Autophagosomal Syntaxin17-dependent lysosomal degradation maintains neuronal function in Drosophila. J Cell Biol. 201(4):531-9.

Erdi B, Nagy P, Zvara A, Varga A, Pircs K, Menesi D, Puskas LG, Juhasz G. (2012) Loss of the starvation-induced gene Rack1 leads to glycogen deficiency and impaired autophagic responses in Drosophila. Autophagy. 8(7):1124-35.

Juhasz G. (2012) Interpretation of bafilomycin, pH neutralizing or protease inhibitor treatments in autophagic flux experiments: novel considerations. Autophagy. 8(12):1875-6.

Juhasz G, Hill JH, Yan Y, Sass M, Baehrecke EH, Backer JM, Neufeld TP. (2008) The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J Cell Biol. 181(4):655-66.

Juhasz G, Erdi B, Sass M, Neufeld TP. (2007) Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Dev. 21(23):3061-6.

Juhasz G, Neufeld TP. (2006) Autophagy: a forty-year search for a missing membrane source. PLoS Biol. 4(2):e36.