Macromitophagy, neutral lipids synthesis, and peroxisomal fatty acid oxidation protect yeast from "liponecrosis", a previously unknown form of programmed cell death

Cell Cycle. 2014;13(1):138-47. doi: 10.4161/cc.26885. Epub 2013 Oct 28.


We identified a form of cell death called "liponecrosis." It can be elicited by an exposure of the yeast Saccharomyces cerevisiae to exogenous palmitoleic acid (POA). Our data imply that liponecrosis is: (1) a programmed, regulated form of cell death rather than an accidental, unregulated cellular process and (2) an age-related form of cell death. Cells committed to liponecrotic death: (1) do not exhibit features characteristic of apoptotic cell death; (2) do not display plasma membrane rupture, a hallmark of programmed necrotic cell death; (3) akin to cells committed to necrotic cell death, exhibit an increased permeability of the plasma membrane for propidium iodide; (4) do not display excessive cytoplasmic vacuolization, a hallmark of autophagic cell death; (5) akin to cells committed to autophagic death, exhibit a non-selective en masse degradation of cellular organelles and require the cytosolic serine/threonine protein kinase Atg1p for executing the death program; and (6) display a hallmark feature that has not been reported for any of the currently known cell death modalities-namely, an excessive accumulation of lipid droplets where non-esterified fatty acids (including POA) are deposited in the form of neutral lipids. We therefore concluded that liponecrotic cell death subroutine differs from the currently known subroutines of programmed cell death. Our data suggest a hypothesis that liponecrosis is a cell death module dynamically integrated into a so-called programmed cell death network, which also includes the apoptotic, necrotic, and autophagic modules of programmed cell death. Based on our findings, we propose a mechanism underlying liponecrosis.

Keywords: apoptosis; autophagic cell death; autophagy; fatty acids; lipid droplets; mechanisms of programmed cell death; mitophagy; necrosis; peroxisomes; yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxyacyl CoA Dehydrogenases / genetics
  • 3-Hydroxyacyl CoA Dehydrogenases / metabolism
  • Acetyl-CoA C-Acyltransferase / genetics
  • Acetyl-CoA C-Acyltransferase / metabolism
  • Carbon-Carbon Double Bond Isomerases / genetics
  • Carbon-Carbon Double Bond Isomerases / metabolism
  • Cell Death / genetics*
  • Enoyl-CoA Hydratase / genetics
  • Enoyl-CoA Hydratase / metabolism
  • Lipids / biosynthesis
  • Lipids / chemistry
  • Mitophagy / genetics*
  • Necrosis / genetics*
  • Peroxisomes / genetics
  • Peroxisomes / metabolism
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development


  • Lipids
  • fatty acid oxidation complex
  • 3-Hydroxyacyl CoA Dehydrogenases
  • Acetyl-CoA C-Acyltransferase
  • Enoyl-CoA Hydratase
  • Racemases and Epimerases
  • Carbon-Carbon Double Bond Isomerases