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Adenosine Triphosphate (ATP) Is a Candidate Signaling Molecule in the Mitochondria-to-Nucleus Retrograde Response Pathway
- Source :
- Genes; Volume 4; Issue 1; Pages: 86-100, Genes, Genes, Vol 4, Iss 1, Pp 86-100 (2013)
- Publication Year :
- 2013
- Publisher :
- MDPI AG, 2013.
-
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.
- Subjects :
- lcsh:QH426-470
retrograde response
Saccharomyces cerevisiae
Oxidative phosphorylation
Mitochondrion
Article
K. waltii
03 medical and health sciences
chemistry.chemical_compound
Mks1
Genetics
Genetics (clinical)
Actin
030304 developmental biology
mitochondria to nucleus signaling
0303 health sciences
ATP synthase
biology
Kinase
030302 biochemistry & molecular biology
K. lactis
ATP sensing
Rtg2
Cell biology
lcsh:Genetics
chemistry
Biochemistry
Retrograde signaling
biology.protein
Adenosine triphosphate
Binding domain
Subjects
Details
- ISSN :
- 20734425
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Genes
- Accession number :
- edsair.doi.dedup.....02479de49ee2385637b1ddfa4d87583d
- Full Text :
- https://doi.org/10.3390/genes4010086