mTOR regulates phagosome and entotic vacuole fission

Matej Krajcovic1, Shefali Krishna, Leila Akkari

  • 1Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065 BCMB Allied Program, Weill Cornell Medical College, New York, NY 10065.

Insights

Phagocytosis and entosis involve vacuole fission, a late maturation step regulated by mTORC1. This process recycles nutrients and membrane, crucial for cell survival and function.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Phagocytosis and entosis are cellular processes involving the engulfment and digestion of cargo within vacuoles.
  • Mechanisms for nutrient export and vacuole membrane processing after cargo digestion are not well understood.

Purpose of the Study:

  • To investigate the late maturation steps of vacuoles formed during phagocytosis and entosis.
  • To identify the regulatory mechanisms governing vacuole membrane processing and nutrient recycling.

Main Methods:

  • Live-cell imaging of phagosomes and entotic vacuoles.
  • Immunofluorescence microscopy to detect protein localization.
  • Biochemical assays to measure nutrient levels and cell survival.

Main Results:

  • Phagosomes and entotic vacuoles undergo a late maturation step involving membrane fission.
  • Vacuole fission is regulated by the mammalian target of rapamycin complex 1 (mTORC1).
  • mTORC1 localizes to vacuole membranes and its activity is sustained by nutrients from digested cargo, promoting cell survival.

Conclusions:

  • A novel late stage of phagocytosis and entosis, characterized by mTORC1-regulated membrane fission, has been identified.
  • This fission process redistributes vacuolar contents into lysosomal networks and facilitates nutrient recycling.
  • The findings highlight the importance of mTORC1 in processing large vacuoles and supporting cell viability during nutrient scarcity.

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