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

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.