Inhibition of autophagy in mitotic animal cells

Eeva Liisa Eskelinen, Alan R. Prescott, Jennifer Cooper, Saskia M. Brachmann, Lijun Wang, Xiuwen Tang, Jonathan M. Backer, John M. Lucocq

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

In nutrient-deprived cells autophagy recycles cytoplasmic constituents by engulfing and degrading them in membrane-bound autophagic vacuoles. The regulation of autophagic vacuole formation is poorly understood, but here we show this process is under strict cell-cycle control in cultured animal cells. We found strong inhibition of autophagic vacuole accumulation in nocodazole-arrested pseudo-prometaphase cells, and also in metaphase and anaphase cells generated on release from the nocodazole arrest. Autophagic vacuoles reappeared after closure of the nuclear envelope in telophase/G1. Treatment with phosphoinositide 3(PI3)-kinase inhibitors wortmannin, LY294002 and 3-methyladenine (known to inhibit the autophagic response in interphase cells) rescued autophagy in mitotic cells without inducing reassembly of vesiculated ER and Golgi compartments. The autophagy induced in mitotic cells was inhibited by amino acids, and the resulting autophagosomes contained proteins LC3 and Lamp1, known to be associated with autophagosomes in interphase cells. The mitotic inhibition of autophagy was not relieved by rapamycin treatment or in PDK1-/-embryonic stem cells, by microinjection of inhibitory antibodies against the class III PI3 kinase VPS34, or in cell lines lacking the p85 regulatory subunits of class IA PI3 kinases. Our results show that autophagy is under strict mitotic control and indicate a novel role for phosphoinositide 3-kinases or other wortmannin/LY294002-sensitive kinases in mitotic membrane traffic regulation.

Original languageEnglish (US)
Pages (from-to)878-893
Number of pages16
JournalTraffic
Volume3
Issue number12
DOIs
StatePublished - Dec 1 2002

Fingerprint

Autophagy
Phosphatidylinositols
Animals
Phosphotransferases
Cells
1-Phosphatidylinositol 4-Kinase
Vacuoles
Nocodazole
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Interphase
Membranes
Sirolimus
Prometaphase
Stem cells
Telophase
Nutrients
Anaphase
Immunoglobulin Isotypes
Nuclear Envelope
Microinjections

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Eskelinen, E. L., Prescott, A. R., Cooper, J., Brachmann, S. M., Wang, L., Tang, X., ... Lucocq, J. M. (2002). Inhibition of autophagy in mitotic animal cells. Traffic, 3(12), 878-893. https://doi.org/10.1034/j.1600-0854.2002.31204.x

Inhibition of autophagy in mitotic animal cells. / Eskelinen, Eeva Liisa; Prescott, Alan R.; Cooper, Jennifer; Brachmann, Saskia M.; Wang, Lijun; Tang, Xiuwen; Backer, Jonathan M.; Lucocq, John M.

In: Traffic, Vol. 3, No. 12, 01.12.2002, p. 878-893.

Research output: Contribution to journalArticle

Eskelinen, EL, Prescott, AR, Cooper, J, Brachmann, SM, Wang, L, Tang, X, Backer, JM & Lucocq, JM 2002, 'Inhibition of autophagy in mitotic animal cells', Traffic, vol. 3, no. 12, pp. 878-893. https://doi.org/10.1034/j.1600-0854.2002.31204.x
Eskelinen EL, Prescott AR, Cooper J, Brachmann SM, Wang L, Tang X et al. Inhibition of autophagy in mitotic animal cells. Traffic. 2002 Dec 1;3(12):878-893. https://doi.org/10.1034/j.1600-0854.2002.31204.x
Eskelinen, Eeva Liisa ; Prescott, Alan R. ; Cooper, Jennifer ; Brachmann, Saskia M. ; Wang, Lijun ; Tang, Xiuwen ; Backer, Jonathan M. ; Lucocq, John M. / Inhibition of autophagy in mitotic animal cells. In: Traffic. 2002 ; Vol. 3, No. 12. pp. 878-893.
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