AMPK phosphorylation of FNIP1 dictates the kinetics of lysosome and mitochondrial biogenesis
Please note this seminar will be held online
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 TFEB-dependent increases of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and estrogen-related receptor alpha (ERRα) messenger RNAs. Thus, mitochondrial damage triggers AMPK-FNIP1-dependent nuclear translocation of TFEB, inducing sequential waves of lysosomal and mitochondrial biogenesis.
Date: 3 August 2023, 15:00
Venue: Online - email hod-pa@dpag.ox.ac.uk for the details
Speaker: Dr Nazma Malik (Salk Institute)
Organising department: Department of Physiology, Anatomy and Genetics (DPAG)
Organiser contact email address: hod-pa@dpag.ox.ac.uk
Host: Professor David Paterson (DPAG, University of Oxford)
Part of: Neuroscience Theme Guest Speakers (DPAG)
Booking required?: Not required
Audience: Members of the University only
Editor: Talitha Smith