Yeast Cells Exposed to Exogenous Palmitoleic Acid Either Adapt to Stress and Survive or Commit to Regulated Liponecrosis and Die

Figure 1

A model for how yeast cells exposed to exogenous palmitoleic acid (POA) either mount a protective stress response and survive or commit to POA-induced regulated liponecrosis and die. Yeast cells briefly exposed to POA can employ four different prosurvival processes to cope with the POA-induced cellular stress and maintain viability. These prosurvival cellular processes include the following: (1) an assimilation of POA into neutral lipids (triacylglycerols (TAGs) and ergosteryl esters (EEs)), in the endoplasmic reticulum (ER) and the subsequent deposition of these neutral lipids in lipid droplets (LD); (2) POA oxidation in peroxisomes (PER); (3) a macroautophagic degradation of dysfunctional or damaged mitochondria (MIT); and (4) a proteolytic degradation of oxidatively damaged, dysfunctional, unfolded, and aggregated proteins that accumulate in the cytosol of yeast cells. Arrows and names displayed in blue color denote prosurvival processes, metabolites, and proteins that protect yeast from POA-induced liponecrotic regulated cell death (RCD). Yeast cells briefly treated with POA can use four different pro-death processes to commit to POA-induced liponecrotic RCD and to execute this RCD subroutine. These pro-death cellular processes include the following: (1) a buildup of POA-containing phospholipids (PLs) in the PM and the ensuing increase in the permeability of the PM to small molecules; (2) the accumulation of POA-containing PLs in both mitochondrial membranes and the resulting decline in mitochondrial functionality, which is needed to support the prosurvival process of incorporating exogenous POA into neutral lipids; (3) a ROS-inflicted oxidative damage to mitochondria and other cellular organelles, which stimulates a nonselective macroautophagic degradation of many kinds of organelles; and (4) a ROS-imposed oxidative damage to cytosolic proteins, which impairs cellular proteostasis because it promotes an accumulation of oxidatively damaged, dysfunctional, unfolded, and aggregated proteins in the cytosol. Arrows and names displayed in red color denote pro-death processes, metabolites, and proteins that commit yeast to POA-induced RCD or execute this RCD subroutine. The up or down arrows in red color denote processes or metabolites whose intensities or concentrations are increased or decreased (resp.) in yeast cells briefly exposed to exogenous POA. See text for more details. ETC, mitochondrial electron transport chain; PE, phosphatidylethanolamine; PLs, phospholipids; PM, plasma membrane; ROS, reactive oxygen species; ΔΨ, electrochemical potential across the inner mitochondrial membrane.