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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
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Mitochondria control mTORC1 activity-linked compartmentalization of eIF4E to regulate extracellular export of

Susanta Chatterjee1, Yogaditya Chakrabarty1, Saikat Banerjee2

  • 1RNA Biology Research Laboratory, Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.

Journal of Cell Science
|December 2, 2020
PubMed

Insights

Mitochondrial dysfunction traps microRNAs (miRNAs) inside cells, hindering their export. Restoring mitochondrial function with Ucp2 inhibition can reverse this, improving miRNA trafficking and release.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Mitochondrial Biology

Background:

  • Defective intracellular trafficking and export of microRNAs (miRNAs) are linked to growth-retarded cells with impaired mitochondrial function.
  • Mitochondrial membrane potential and dynamics play a crucial role in cellular processes.

Purpose of the Study:

  • To investigate the link between mitochondrial dysfunction and miRNA trafficking defects.
  • To identify mechanisms regulating miRNA export and subcellular localization.

Main Methods:

  • Studied growth-retarded mammalian cells with impaired mitochondrial potential.
  • Utilized uncoupling protein 2 (Ucp2) inhibition with Genipin.
  • Analyzed miRNA sequestration in polysomes and release via extracellular vesicles.
  • Investigated mitochondrial-ER tethering and translation initiation factor eIF4E compartmentalization.
  • Assessed mammalian target of rapamycin complex 1 (mTORC1) activity and eIF4E-BP1 phosphorylation.

Main Results:

  • Ucp2-mediated mitochondrial depolarization caused miRNA sequestration in polysomes and reduced extracellular export.
  • Mitochondrial dysfunction led to endoplasmic reticulum (ER) detethering, impairing eIF4E compartmentalization to ER-attached polysomes.
  • Reduced mTORC1 activity in dysfunctional cells prevented eIF4E targeting to polysomes, hindering miRNA export.
  • Genipin treatment reversed these defects in growth-retarded human cells.

Conclusions:

  • Mitochondrial membrane potential and dynamics regulate miRNA subcellular localization and export by influencing mTORC1 activity and compartmentalization.
  • Defective mitochondrial-ER tethering disrupts translation initiation factor localization, leading to miRNA retention.
  • Targeting Ucp2 offers a potential strategy to restore miRNA trafficking in cellular growth defects.
Keywords:
ExosomesExtracellular vesiclesMitochondriaP-bodyPolysomeProcessing bodieseIF4EmTORC1miRNA

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