Induction of lysosomal and mitochondrial biogenesis by AMPK phosphorylation of FNIP1

Cells respond to mitochondrial poisons with rapid activation of the adenosine monophosphate-activated protein kinase (AMPK), causing acute metabolic changes through phosphorylation and prolonged adaptation of metabolism through transcriptional effects. Transcription factor EB (TFEB) is a major effector of AMPK that increases expression of lysosome genes in response to energetic stress, but how AMPK activates TFEB remains unresolved. We demonstrate that AMPK directly phosphorylates five conserved serine residues in folliculin-interacting protein 1 (FNIP1), suppressing the function of the folliculin (FLCN)-FNIP1 complex. FNIP1 phosphorylation is required for AMPK to induce nuclear translocation of TFEB and…

• NS
  National Science Foundation
• AH
  American Heart Association

  Award: 19PABH134610000
• GF
  Glenn Foundation for Medical Research
• LM
  Leona M. and Harry B. Helmsley Charitable Trust

  Awards: 2012-PG-MED002, MED002
• WF
  Waitt Foundation
• NI
  National Institutes of Health

  Awards: R35CA220538, CA014195, CCSG P30 CA014195, R21 DC018237, P01CA120964, P30 CA014195, R01DK080425, CCSG P30, P30 AG068635
• NC
  National Cancer Institute

  Awards: CA014195, P30 CA014195, P01CA120964