HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 52, 42528-42535, December 30, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/52/42528    most recent M509187200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giannattasio, S. Articles by Butow, R. A. Search for Related Content PubMed PubMed Citation Articles by Giannattasio, S. Articles by Butow, R. A. Social Bookmarking                      What's this?

Retrograde Response to Mitochondrial Dysfunction Is Separable from TOR1/2 Regulation of Retrograde Gene Expression^*

Sergio Giannattasio, Zhengchang Liu, Janet Thornton, and Ronald A. Butow1

From the Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9148 and Consiglio Nazionale delle Ricerche, Istituto di Biomembrane e Bioenergetica, Via Amendola 165/A, I-70126 Bari, Italy

Retrograde (RTG) signaling senses mitochondrial dysfunction and initiates readjustments of carbohydrate and nitrogen metabolism through nuclear accumulation of the heterodimeric transcription factors, Rtg1/3p. The RTG pathway is also linked to target of rapamycin (TOR) signaling, among whose activities is transcriptional control of nitrogen catabolite repression (NCR)-sensitive genes. To investigate the connections between these two signaling pathways, we have analyzed rapamycin sensitivity of the expression of the RTG target gene CIT2 and of two NCR-sensitive genes, GLN1 and DAL5, in respiratory-competent (⁺) and -incompetent (⁰) yeast cells. Here we have presented evidence that retrograde gene expression is separable from TOR regulation of RTG- and NCR-responsive genes. We showed that expression of these two classes of genes is differentially regulated by glutamate starvation whether in response to mitochondrial dysfunction or induced by rapamycin treatment, as well by glutamine or histidine starvation. We also showed that Lst8p, a component of the TOR1/2 complexes and a negative regulator of the RTG pathway, has multiple roles in the regulation of RTG- and NCR-sensitive genes. Lst8p negatively regulates CIT2 and GLN1 expression, whereas DAL5 expression is independent of Lst8p function. DAL5 expression depends on the GATA transcription factors Gln3p and Gat1p. Gat1p is translocated to the nucleus only upon TOR inhibition by rapamycin. Altogether, these data show that Rtg1/3p, Gln3p, and Gat1p can be differentially regulated through different nutrient-sensing pathways, such as TOR and retrograde signaling, and by multiple factors, such as Lst8p, which is suggested to have a role in connecting the RTG and TOR pathways.

Received for publication, August 19, 2005 , and in revised form, October 19, 2005.

^* This work was supported by National Institutes of Health Grant GM22525 and Grant I-0642 from The Robert A. Welch Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Molecular Biology, UT Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148. Tel.: 214-648-1465; Fax: 214-648-1488; E-mail: Ronald.Butow{at}UTSouthwestern.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Georis, A. Feller, J. J. Tate, T. G. Cooper, and E. Dubois Nitrogen Catabolite Repression-Sensitive Transcription as a Readout of Tor Pathway Regulation: The Genetic Background, Reporter Gene and GATA Factor Assayed Determine the Outcomes Genetics, March 1, 2009; 181(3): 861 - 874. [Abstract] [Full Text] [PDF]

				J. J. Tate, I. Georis, A. Feller, E. Dubois, and T. G. Cooper Rapamycin-induced Gln3 Dephosphorylation Is Insufficient for Nuclear Localization: Sit4 AND PP2A PHOSPHATASES ARE REGULATED AND FUNCTION DIFFERENTLY J. Biol. Chem., January 23, 2009; 284(4): 2522 - 2534. [Abstract] [Full Text] [PDF]

				K. H. Wong, M. J. Hynes, and M. A. Davis Recent Advances in Nitrogen Regulation: a Comparison between Saccharomyces cerevisiae and Filamentous Fungi Eukaryot. Cell, June 1, 2008; 7(6): 917 - 925. [Full Text] [PDF]

				I. Georis, J. J. Tate, T. G. Cooper, and E. Dubois Tor Pathway Control of the Nitrogen-responsive DAL5 Gene Bifurcates at the Level of Gln3 and Gat1 Regulation in Saccharomyces cerevisiae J. Biol. Chem., April 4, 2008; 283(14): 8919 - 8929. [Abstract] [Full Text] [PDF]

				H. Cai, M. Hauser, F. Naider, and J. M. Becker Differential Regulation and Substrate Preferences in Two Peptide Transporters of Saccharomyces cerevisiae Eukaryot. Cell, October 1, 2007; 6(10): 1805 - 1813. [Abstract] [Full Text] [PDF]

				J. J. Tate, A. Feller, E. Dubois, and T. G. Cooper Saccharomyces cerevisiae Sit4 Phosphatase Is Active Irrespective of the Nitrogen Source Provided, and Gln3 Phosphorylation Levels Become Nitrogen Source-responsive in a sit4-deleted Strain J. Biol. Chem., December 8, 2006; 281(49): 37980 - 37992. [Abstract] [Full Text] [PDF]

				M. N. Sack Mitochondrial depolarization and the role of uncoupling proteins in ischemia tolerance Cardiovasc Res, November 1, 2006; 72(2): 210 - 219. [Abstract] [Full Text] [PDF]

				J. J. Tate, R. Rai, and T. G. Cooper Ammonia-specific Regulation of Gln3 Localization in Saccharomyces cerevisiae by Protein Kinase Npr1 J. Biol. Chem., September 22, 2006; 281(38): 28460 - 28469. [Abstract] [Full Text] [PDF]