Mitochondrial Genomic Dysfunction Causes Dephosphorylation of Sch9 in the Yeast Saccharomyces cerevisiae

Kawai, Shigeyuki; Urban, Joerg; Piccolis, Manuele; Panchaud, Nicolas; Virgilio, Claudio De; Loewith, Robbie

doi:10.1128/ec.05157-11

Cited by 31 publications

(23 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondrial dysfunction caused by mitochondrial genomic defects leads to downregulation of TORC1 (Jazwinski and Kriete, 2012;Kawai et al, 2011). Interestingly, the retrograde signaling pathway has been found to be deregulated in NPR2 and NPR3 deletion mutants (Neklesa and Davis, 2009).…”

Section: Modulation Of Nitrogen Metabolism By the Sea Complexmentioning

confidence: 99%

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

Dokudovskaya

Rout

2015

Journal of Cell Science

View full text Add to dashboard Cite

Cells constantly adapt to various environmental changes and stresses. The way in which nutrient and stress levels in a cell feed back to control metabolism and growth are, unsurprisingly, extremely complex, as responding with great sensitivity and speed to the 'feast or famine, slack or stress' status of its environment is a central goal for any organism. The highly conserved target of rapamycin complex 1 (TORC1) controls eukaryotic cell growth and response to a variety of signals, including nutrients, hormones and stresses, and plays the key role in the regulation of autophagy. A lot of attention has been paid recently to the factors in this pathway functioning upstream of TORC1. In this Commentary, we focus on a major, newly discovered upstream regulator of TORC1 -the multiprotein SEA complex, also known as GATOR. We describe the structural and functional features of the yeast complex and its mammalian homolog, and their involvement in the regulation of the TORC1 pathway and TORC1-independent processes. We will also provide an overview of the consequences of GATOR deregulation in cancer and other diseases.

show abstract

Section: Modulation Of Nitrogen Metabolism By the Sea Complexmentioning

confidence: 99%

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

Dokudovskaya

Rout

2015

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…TORC1-mediated phosphorylation of the AGC protein kinase, Sch9, is down-regulated in ρ 0 cells 27 . Phosphorylation of Sch9 directly counteracts the induction of stress responses under the control of the transcription factor Msn2-Msn4, and it also promotes ribosome biogenesis 28 .…”

Section: The Retrograde Signaling Pathwaymentioning

confidence: 96%

The Retrograde Response

Jazwinski

2014

Progress in Molecular Biology and Translational Science

View full text Add to dashboard Cite

The retrograde response was discovered in Saccharomyces cerevisiae as a signaling pathway from the mitochondrion to the nucleus that triggers an array of gene regulatory changes in the latter. The activation of the retrograde response compensates for the deficits associated with aging, and thus it extends yeast replicative lifespan. The retrograde response is activated by the progressive decline in mitochondrial membrane potential during aging that is the result of increasing mitochondrial dysfunction. The ensuing metabolic adaptations and stress resistance can only delay the inevitable demise of the yeast cell. The retrograde response is embedded in a network of signal transduction pathways that impinge upon virtually every aspect of cell physiology. Thus, its manifestations are complicated. Many of these pathways have been implicated in lifespan regulation quite independently of the retrograde response. Together, they operate in a delicate balance in promoting longevity. The retrograde response is closely aligned with cell quality control, often performing when quality control is not sufficient to assure longevity. Among the key pathways related to this aspect of retrograde signaling are target of rapamycin (TOR) and ceramide signaling. The retrograde response can also be found in other organisms, including Caenorhabditis elegans, Drosophila melanogaster, mouse, and human, where it exhibits an ever increasing complexity that may be corralled by the transcription factor NFκB. The retrograde response may have evolved as a cytoprotective mechanism that senses and defends the organism from pathogens and environmental toxins.

show abstract

“…TORC1 phosphorylates the AGC protein kinase Sch9, and this is markedly reduced in cells in which retrograde signaling activity occurs (Kawai, et al, 2011). This has important consequences, as phosphorylation of Sch9 inhibits the activation of stress responses dependent on the Msn2-Msn4 transcription factor, while activating ribosome biogenesis (Urban, et al, 2007).…”

Section: Crosstalk Of Retrograde Signaling With Other Signaling Pamentioning

confidence: 99%

Mitochondria to nucleus signaling and the role of ceramide in its integration into the suite of cell quality control processes during aging

Jazwinski

2015

Ageing Research Reviews

View full text Add to dashboard Cite

Mitochondria to nucleus signaling has been the most extensively studied mode of inter-organelle communication. The first signaling pathway in this category of information transfer to be discovered was the retrograde response, with its own set of signal transduction proteins. The finding that this pathway compensates for mitochondrial dysfunction to extend the replicative lifespan of yeast cells has generated additional impetus for its study. This research has demonstrated crosstalk between the retrograde response and the target of rapamycin (TOR), small GTPase RAS, and high-osmolarity glycerol (HOG) pathways in yeast, all of which are key players in replicative lifespan. More recently, the retrograde response has been implicated in the diauxic shift and survival in stationary phase, extending its operation to the yeast chronological lifespan as well. In this capacity, the retrograde response may cooperate with other, related mitochondria to nucleus signaling pathways. Counterparts of the retrograde response are found in the roundworm, the fruit fly, the mouse, and even in human cells in tissue culture. The exciting realization that the retrograde response is embedded in the network of cellular quality control processes has emerged over the past few years. Most strikingly, it is closely integrated with autophagy and the selective brand of this quality control process, mitophagy. This coordination depends on TOR, and it engages ceramide/sphingolipid signaling. The yeast LAG1 ceramide synthase gene was the first longevity gene cloned as such, and its orthologs hyl-1 and hyl-2 determine worm lifespan. Thus, the involvement of ceramide signaling in quality control gives these findings cellular context. The retrograde response and ceramide are essential components of a lifespan maintenance process that likely evolved as a cytoprotective mechanism to defend the organism from diverse stressors.

show abstract

Mitochondrial Genomic Dysfunction Causes Dephosphorylation of Sch9 in the Yeast Saccharomyces cerevisiae

Cited by 31 publications

References 29 publications

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

SEA you later alli-GATOR – a dynamic regulator of the TORC1 stress response pathway

The Retrograde Response

Mitochondria to nucleus signaling and the role of ceramide in its integration into the suite of cell quality control processes during aging

Contact Info

Product

Resources

About