The nuclear cofactor DOR regulates autophagy in mammalian and Drosophila cells

Caroline Mauvezin, Meritxell Orpinell, Víctor A. Francis, Francisco Mansilla, Jordi Duran, Vicent Ribas, Manuel Palacín, Patricia Boya, Aurelio A. Teleman, Antonio Zorzano

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

The regulation of autophagy in metazoans is only partly understood, and there is a need to identify the proteins that control this process. The diabetes-and obesity-regulated gene (DOR), a recently reported nuclear cofactor of thyroid hormone receptors, is expressed abundantly in metabolically active tissues such as muscle. Here, we show that DOR shuttles between the nucleus and the cytoplasm, depending on cellular stress conditions, and re-localizes to autophagosomes on autophagy activation. We demonstrate that DOR interacts physically with autophagic proteins Golgi-associated ATPase enhancer of 16 kDa (GATE16) and microtubule-associated protein 1A/1B-light chain 3. Gain-of-function and loss-of-function studies indicate that DOR stimulates autophagosome formation and accelerates the degradation of stable proteins. CG11347, the DOR Drosophila homologue, has been predicted to interact with the Drosophila Atg8 homologues, which suggests functional conservation in autophagy. Flies lacking CG11347 show reduced autophagy in the fat body during pupal development. All together, our data indicate that DOR regulates autophagosome formation and protein degradation in mammalian and Drosophila cells.

Original languageEnglish (US)
Pages (from-to)37-44
Number of pages8
JournalEMBO Reports
Volume11
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Keywords

  • Fat body
  • GATE16
  • LC3
  • Nuclear co-regulator
  • Protein degradation

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