An interrelationship between autophagy and filamentous growth in budding yeast.
Over the last 15 years, yeast pseudohyphal growth (PHG) has been the focus of intense research interest as a model of fungal pathogenicity. Specifically, PHG is a stress response wherein yeast cells deprived of nitrogen form filaments of elongated cells. Nitrogen limitation also induces autophagy, a ubiquitous eukaryotic stress response in which proteins are trafficked to the vacuole/lysosome for degradation and recycling. Although autophagy and filamentous growth are both responsive to nitrogen stress, a link between these processes has not been investigated to date. Here, we present several studies describing an interrelationship between autophagy and filamentous growth. By microarray-based expression profiling, we detect extensive upregulation of the pathway governing autophagy during early PHG and find both processes active under conditions of nitrogen stress in a filamentous strain of budding yeast. Inhibition of autophagy results in increased PHG, and autophagy-deficient yeast induce PHG at higher concentrations of available nitrogen. Our results suggest a model in which autophagy mitigates nutrient stress, delaying the onset of PHG; conversely, inhibition of autophagy exacerbates nitrogen stress, resulting in precocious and overactive PHG. This physiological connection highlights the central role of autophagy in regulating the cell's nutritional state and the responsiveness of PHG to that state.
Ma
Jun
J
Department of Molecular, Cellular, and Developmental Biology and Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
Jin
Rui
R
Jia
Xiaoyu
X
Dobry
Craig J
CJ
Wang
Li
L
Reggiori
Fulvio
F
Zhu
Ji
J
Kumar
Anuj
A
D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D015153:Blotting, Western; D002470:Cell Survival; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D025301:Hyphae / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009584:Nitrogen; D020411:Oligonucleotide Array Sequence Analysis; D010588:Phagosomes; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D004718:Saccharomycetales / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
C113757:ATG8 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; C477823:ATG1 protein, S cerevisiae; D009584:Nitrogen