Drosophila Fip200 is an essential regulator of autophagy that attenuates both growth and aging

Autophagy. 2013 Aug;9(8):1201-13. doi: 10.4161/auto.24811. Epub 2013 May 14.


Autophagy-related 1 (Atg1)/Unc-51-like protein kinases (ULKs) are evolutionarily conserved proteins that play critical physiological roles in controlling autophagy, cell growth and neurodevelopment. RB1-inducible coiled-coil 1 (RB1CC1), also known as PTK2/FAK family-interacting protein of 200 kDa (FIP200) is a recently discovered binding partner of ULK1. Here we isolated the Drosophila RB1CC1/FIP200 homolog (Fip200/CG1347) and showed that it mediates Atg1-induced autophagy as a genetically downstream component in diverse physiological contexts. Fip200 loss-of-function mutants experienced severe mobility loss associated with neuronal autophagy defects and neurodegeneration. The Fip200 mutants were also devoid of both developmental and starvation-induced autophagy in salivary gland and fat body, while having no defects in axonal transport and projection in developing neurons. Interestingly, moderate downregulation of Fip200 accelerated both developmental growth and aging, accompanied by target of rapamycin (Tor) signaling upregulation. These results suggest that Fip200 is a critical downstream component of Atg1 and specifically mediates Atg1's autophagy-, aging- and growth-regulating functions.

Keywords: Drosophila; aging; autophagy; growth; neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Autophagy*
  • Autophagy-Related Protein-1 Homolog
  • Axons / metabolism
  • Axons / pathology
  • Brain / metabolism
  • Brain / pathology
  • Conserved Sequence
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / growth & development*
  • Drosophila melanogaster / metabolism*
  • Drosophila melanogaster / ultrastructure
  • Homeostasis
  • Motor Activity
  • Mutation / genetics
  • Nerve Degeneration / pathology
  • Protein Serine-Threonine Kinases / metabolism
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Time Factors
  • Ubiquitin / metabolism
  • Vacuoles / metabolism
  • Vacuoles / ultrastructure


  • Atg17 protein, Drosophila
  • Drosophila Proteins
  • Ubiquitin
  • Atg1 protein, Drosophila
  • Autophagy-Related Protein-1 Homolog
  • Protein Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases