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Updated: Jun 28, 2026
05:30
Live-cell Imaging of Lysosomal Membrane Permeabilization During Necroptosis
Published on: November 14, 2025
Necrotic cell death: From reversible mitochondrial uncoupling to irreversible lysosomal permeabilization
Corinne Giusti1, Marie-Françoise Luciani, Gérard Klein
1Centre d'Immunologie de Marseille-Luminy (CIML), Faculté des Sciences de Luminy, Aix Marseille Université, Marseille F-13288, France.
Experimental Cell Research
|October 28, 2008
Summary
Necrotic cell death (NCD) in Dictyostelium involves a reversible mitochondrial-lysosomal cascade. Lysosomal permeabilization marks an irreversible stage, requiring sustained uncoupler presence for mitochondrial and lysosomal damage.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Dictyostelium atg1- mutant cells offer a model for studying necrotic cell death (NCD) without apoptosis or autophagy.
- Mitochondrial uncoupling initiates NCD in these cells upon starvation and cAMP induction.
Purpose of the Study:
- To elucidate the mitochondrial-lysosomal cascade in NCD.
- To investigate the reversibility of NCD stages.
- To define NCD at the lysosomal level.
Main Methods:
- Utilized Dictyostelium atg1- mutant cells.
- Induced NCD using differentiation-inducing factor (DIF) or uncouplers.
- Assessed mitochondrial uncoupling and lysosomal permeabilization using specific dyes and substrates (Lysosensor blue, acridin orange, Texas red-dextran, cathepsin B substrate).
Main Results:
- NCD involves a mitochondrial-lysosomal cascade.
- Early stages of mitochondrial uncoupling were reversible.
- Lysosomal permeabilization was demonstrated and found to be irreversible.
- Continuous presence of the uncoupler was necessary for both mitochondrial and lysosomal lesions.
Conclusions:
- Characterized the NCD pathway in Dictyostelium, highlighting a mitochondrial-lysosomal cascade.
- Defined NCD at the lysosomal level, identifying irreversible permeabilization as a key event.
- Suggests potential therapeutic strategies targeting late-stage reversibility in mammalian NCD.
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