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

ABSTRACT: 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 tr

SUBMITTER: Rockenfeller P 

PROVIDER: S-EPMC5864183 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature