Deadly Encounter: Endosomes Meet Mitochondria to Initiate Apoptosis

Mariella Vicinanza1, David C Rubinsztein1

  • 1Cambridge Institute for Medical Research, Department of Medical Genetics, The Keith Peters Building, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK; UK Dementia Research Institute, Cambridge BioMedical Campus, The Keith Peters Building, Hills Road, Cambridge CB2 0XY, UK.

Developmental Cell
|June 24, 2020
PubMed

Insights

Apoptotic cell death relies on mitochondrial outer membrane permeabilization (MOMP). New research shows endosomes accumulating on mitochondria trigger lipid changes, aiding MOMP pore formation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondrial outer membrane permeabilization (MOMP) is a critical step in programmed cell death (apoptosis).
  • The precise mechanisms regulating the full execution of MOMP are not completely understood.
  • Endosomes are known to play roles in various cellular processes, but their involvement in MOMP is less explored.

Purpose of the Study:

  • To investigate the role of endosomes in the execution of MOMP.
  • To identify molecular interactions that facilitate MOMP.
  • To understand how mitochondrial lipid alterations contribute to apoptotic pore assembly.

Main Methods:

  • Cellular imaging techniques to observe mitochondria and endosomes during apoptosis.
  • Biochemical assays to analyze mitochondrial lipid composition.
  • Co-immunoprecipitation to identify protein interactions between endosomes and mitochondria.

Main Results:

  • Endosomes were observed to accumulate on mitochondria undergoing MOMP.
  • This accumulation led to significant alterations in mitochondrial lipid profiles.
  • A novel interaction was identified that links endosome accumulation to mitochondrial lipid changes, facilitating pore formation.

Conclusions:

  • Endosome accumulation on apoptotic mitochondria is essential for the complete execution of MOMP.
  • Mitochondrial lipid alterations induced by endosomes are key events in functional pore assembly.
  • This study reveals a new mechanism controlling a critical step in programmed cell death.

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