Next Article in Journal / Special Issue
The Role of Mitogen-Activated Protein Kinase-Activated Protein Kinases (MAPKAPKs) in Inflammation
Previous Article in Journal / Special Issue
Gene Expressions for Signal Transduction under Acidic Conditions
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Adenosine Triphosphate (ATP) Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway

1
Department of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA
2
Department of Biological Sciences, University of New Orleans, 2000 Lakeshore Drive, New Orleans, LA 70148, USA
*
Author to whom correspondence should be addressed.
Division of Molecular Medicine & Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Current address: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Genes 2013, 4(1), 86-100; https://doi.org/10.3390/genes4010086
Submission received: 4 February 2013 / Revised: 9 March 2013 / Accepted: 15 March 2013 / Published: 20 March 2013
(This article belongs to the Special Issue Signal Transduction)

Abstract

Intracellular communication from the mitochondria to the nucleus is achieved via the retrograde response. In budding yeast, the retrograde response, also known as the RTG pathway, is regulated positively by Rtg1, Rtg2, Rtg3 and Grr1 and negatively by Mks1, Lst8 and two 14-3-3 proteins, Bmh1/2. Activation of retrograde signaling leads to activation of Rtg1/3, two basic helix-loop-helix leucine zipper transcription factors. Rtg1/3 activation requires Rtg2, a cytoplasmic protein with an N-terminal adenosine triphosphate (ATP) binding domain belonging to the actin/Hsp70/sugar kinase superfamily. The critical regulatory step of the retrograde response is the interaction between Rtg2 and Mks1. Rtg2 binds to and inactivates Mks1, allowing for activation of Rtg1/3 and the RTG pathway. When the pathway is inactive, Mks1 has dissociated from Rtg2 and bound to Bmh1/2, preventing activation of Rtg1/3. What signals association or disassociation of Mks1 and Rtg2 is unknown. Here, we show that ATP at physiological concentrations dissociates Mks1 from Rtg2 in a highly cooperative fashion. We report that ATP-mediated dissociation of Mks1 from Rtg2 is conserved in two other fungal species, K. lactis and K. waltii. Activation of Rtg1/3 upregulates expression of genes encoding enzymes catalyzing the first three reactions of the Krebs cycle, which is coupled to ATP synthesis through oxidative phosphorylation. Therefore, we propose that the retrograde response is an ATP homeostasis pathway coupling ATP production with ATP-mediated repression of the retrograde response by releasing Mks1 from Rtg2.
Keywords: retrograde response; mitochondria to nucleus signaling; Rtg2; Mks1; ATP sensing; Saccharomyces cerevisiae; K. lactis; K. waltii retrograde response; mitochondria to nucleus signaling; Rtg2; Mks1; ATP sensing; Saccharomyces cerevisiae; K. lactis; K. waltii
Graphical Abstract

Share and Cite

MDPI and ACS Style

Zhang, F.; Pracheil, T.; Thornton, J.; Liu, Z. Adenosine Triphosphate (ATP) Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway. Genes 2013, 4, 86-100. https://doi.org/10.3390/genes4010086

AMA Style

Zhang F, Pracheil T, Thornton J, Liu Z. Adenosine Triphosphate (ATP) Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway. Genes. 2013; 4(1):86-100. https://doi.org/10.3390/genes4010086

Chicago/Turabian Style

Zhang, Feng, Tammy Pracheil, Janet Thornton, and Zhengchang Liu. 2013. "Adenosine Triphosphate (ATP) Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway" Genes 4, no. 1: 86-100. https://doi.org/10.3390/genes4010086

APA Style

Zhang, F., Pracheil, T., Thornton, J., & Liu, Z. (2013). Adenosine Triphosphate (ATP) Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway. Genes, 4(1), 86-100. https://doi.org/10.3390/genes4010086

Article Metrics

Back to TopTop