An mTORC1-to-CDK1 Switch Maintains Autophagy Suppression during Mitosis.
Mol Cell
; 77(2): 228-240.e7, 2020 01 16.
Article
em En
| MEDLINE
| ID: mdl-31733992
ABSTRACT
Since nuclear envelope breakdown occurs during mitosis in metazoan cells, it has been proposed that macroautophagy must be inhibited to maintain genome integrity. However, repression of macroautophagy during mitosis remains controversial and mechanistic detail limited to the suggestion that CDK1 phosphorylates VPS34. Here, we show that initiation of macroautophagy, measured by the translocation of the ULK complex to autophagic puncta, is repressed during mitosis, even when mTORC1 is inhibited. Indeed, mTORC1 is inactive during mitosis, reflecting its failure to localize to lysosomes due to CDK1-dependent RAPTOR phosphorylation. While mTORC1 normally represses autophagy via phosphorylation of ULK1, ATG13, ATG14, and TFEB, we show that the mitotic phosphorylation of these autophagy regulators, including at known repressive sites, is dependent on CDK1 but independent of mTOR. Thus, CDK1 substitutes for inhibited mTORC1 as the master regulator of macroautophagy during mitosis, uncoupling autophagy regulation from nutrient status to ensure repression of macroautophagy during mitosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Proteína Quinase CDC2
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Alvo Mecanístico do Complexo 1 de Rapamicina
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Mitose
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Mol Cell
Ano de publicação:
2020
Tipo de documento:
Article