The Rim101 pathway contributes to ER stress adaptation through sensing the state of plasma membrane

Obara, Keisuke; Kihara, Akio

doi:10.1042/bcj20160580

Cited by 14 publications

(13 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6g ). Rim101 activation through manipulation of plasma membrane lipids has been reported to depend on the Rim21 sensor complex which includes RIM21 , RIM9 , DFG16 , and RIM8 [ 26 , 27 ]. This raised the question whether DG-induced cell death would also depend on this sensor complex.…”

Section: Resultsmentioning

confidence: 99%

Diacylglycerol triggers Rim101 pathway–dependent necrosis in yeast: a model for lipotoxicity

et al. 2018

View full text Add to dashboard Cite

The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyl-sn-glycerol (DOG) triggers necrotic cell death. The toxic effects of DG are linked to glucose metabolism and require a functional Rim101 signaling cascade involving the Rim21-dependent sensing complex and the activation of a calpain-like protease. The Rim101 cascade is an established pathway that triggers a transcriptional response to alkaline or lipid stress. We propose that the Rim101 pathway senses DG-induced lipid perturbation and conducts a signaling response that either facilitates cellular adaptation or triggers lipotoxic cell death. Using established models of lipotoxicity, i.e., high-fat diet in Drosophila and palmitic acid administration in cultured human endothelial cells, we present evidence that the core mechanism underlying this calpain-dependent lipotoxic cell death pathway is phylogenetically conserved.

show abstract

Section: Resultsmentioning

confidence: 99%

Diacylglycerol triggers Rim101 pathway–dependent necrosis in yeast: a model for lipotoxicity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The latter option has recently been introduced by Obara and Kihara. They found that Rim101 signalling can be triggered by ER stress (Obara and Kihara 2017 ). ER stress can affect lipid asymmetry and thus Rim101 could be triggered in order to compensate for these changes.…”

Section: Sensing Lipid Stress At the Pmmentioning

confidence: 99%

“…A recent study investigated whether Rim101 signalling depends on ER-PM contact sites (Obara and Kihara 2017 ). The authors revealed that Rim101 signalling occurred mostly at sites different from ER–PM contact sites.…”

Section: The Role Of Mcs In Lipotoxicitymentioning

confidence: 99%

Lipotoxicty in yeast: a focus on plasma membrane signalling and membrane contact sites

Rockenfeller

Gourlay

2018

FEMS Yeast Research

View full text Add to dashboard Cite

Lipotoxicity is a pathophysiological process triggered by lipid overload. In metazoans, lipotoxicity is characterised by the ectopic deposition of lipids on organs other than adipose tissue. This leads to organ dysfunction, cell death, and is intimately linked to lipid-associated diseases such as cardiac dysfunction, atherosclerosis, stroke, hepatosteatosis, cancer and the metabolic syndrome. The molecules involved in eliciting lipotoxicity include FAs and their acyl-CoA derivatives, triacylglycerol (TG), diacylglycerol (DG), ceramides, acyl-carnitines and phospholipids. However, the cellular transport of toxic lipids through membrane contact sites (MCS) and vesicular mechanisms as well as lipid metabolism that progress lipotoxicity to the onset of disease are not entirely understood. Yeast has proven a useful model organism to study the molecular mechanisms of lipotoxicity. Recently, the Rim101 pathway, which senses alkaline pH and the lipid status at the plasmamembrane, has been connected to lipotoxicity. In this review article, we summarise recent research advances on the Rim101 pathway and MCS in the context of lipotoxicity in yeast and present a perspective for future research directions.

show abstract

“…Several observations indicate that alterations in lipid homeostasis induce mechanisms involved in protein quality control. Conditions that perturb lipid biosynthesis, that alter the lipid compositions of the plasma membrane and endomembranes or that affect the lipid droplet content of cells were all reported to trigger ER stress and activation of the unfolded protein response (UPR) 182 183 184 185 186 187 188 . In contrast to acute ER stress, which induces PCD 189 190 , the lipid-associated induction of ER stress appears to be linked to compensatory mechanisms directed to reinstate lipid biosynthesis and lipid metabolism and to promote cell survival 191 192 193 194 195 .…”

Section: Ph Control Stress Tolerance and Longevitymentioning

confidence: 99%

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

Deprez¹,

Eskes²,

Wilms³

et al. 2018

Microb Cell

View full text Add to dashboard Cite

The plasma membrane H+-ATPase Pma1 and the vacuolar V-ATPase act in close harmony to tightly control pH homeostasis, which is essential for a vast number of physiological processes. As these main two regulators of pH are responsive to the nutritional status of the cell, it seems evident that pH homeostasis acts in conjunction with nutrient-induced signalling pathways. Indeed, both PKA and the TORC1-Sch9 axis influence the proton pumping activity of the V-ATPase and possibly also of Pma1. In addition, it recently became clear that the proton acts as a second messenger to signal glucose availability via the V-ATPase to PKA and TORC1-Sch9. Given the prominent role of nutrient signalling in longevity, it is not surprising that pH homeostasis has been linked to ageing and longevity as well. A first indication is provided by acetic acid, whose uptake by the cell induces toxicity and affects longevity. Secondly, vacuolar acidity has been linked to autophagic processes, including mitophagy. In agreement with this, a decline in vacuolar acidity was shown to induce mitochondrial dysfunction and shorten lifespan. In addition, the asymmetric inheritance of Pma1 has been associated with replicative ageing and this again links to repercussions on vacuolar pH. Taken together, accumulating evidence indicates that pH homeostasis plays a prominent role in the determination of ageing and longevity, thereby providing new perspectives and avenues to explore the underlying molecular mechanisms.

show abstract

The Rim101 pathway contributes to ER stress adaptation through sensing the state of plasma membrane

Cited by 14 publications

References 44 publications

Diacylglycerol triggers Rim101 pathway–dependent necrosis in yeast: a model for lipotoxicity

Diacylglycerol triggers Rim101 pathway–dependent necrosis in yeast: a model for lipotoxicity

Lipotoxicty in yeast: a focus on plasma membrane signalling and membrane contact sites

pH homeostasis links the nutrient sensing PKA/TORC1/Sch9 ménage-à-trois to stress tolerance and longevity

Contact Info

Product

Resources

About