title: Transcriptional regulation of ATG9 by the Pho23-Rpd3 complex modulates the frequency of autophagosome formation.
abstract: Studies of the physiological and pathological roles of autophagy have revealed that too little or too much autophagy can be detrimental, and therefore autophagy activity needs to be tightly regulated. Altered transcription of autophagy-related (ATG) genes has been reported in many diseases, and ATG genes can be the most direct targets for the treatment of autophagy-associated diseases. Thus, it is important to understand how the amounts of different Atg proteins affect autophagy, and how the expression of their corresponding genes is regulated. Using budding yeast as the model, we showed that Pho23, a component of the Rpd3 large (Rpd3L) complex, represses the transcription of several ATG genes including ATG9, the expression of which regulates the frequency of autophagosome formation. More autophagosomes are formed in PHO23 null cells or in those overexpressing Atg9; conversely, there are fewer autophagosomes seen in cells with reduced Atg9 expression.
authors.affiliation: Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology; University of Michigan; Ann Arbor, MI USA.
authors.forename: Meiyan
authors.initials: M
authors.lastname: Jin
authors.affiliation: Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology; University of Michigan; Ann Arbor, MI USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Klionsky
mesh_terms: D001343:Autophagy / Q000502:physiology; D000071183:Autophagy-Related Proteins; D005786:Gene Expression Regulation / Q000502:physiology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014158:Transcription, Genetic; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C574794:ATG9A protein, human; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; C432409:Pho23 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases
keywords: autophagy; lysosome; phagophore; stress; vacuole; yeast