O-GlcNAcylation suppresses TRAP1 activity and promotes mitochondrial respiration

Activation of autophagy depends on Atg1/Ulk1-mediated phosphorylation and inhibition of the Hsp90 chaperone machinery

“…PLA was performed using manufacturers protocol (Sigma-Aldrich) as previously described. 90 HEK293 cells were plated overnight on glass coverslips and then transiently transfected with pcDNA3-EV, pcDNA3-hHsp90α-FLAG-WT, S39A or S39E overnight. Cells were fixed in 4% paraformaldehyde for 20 min at room temperature, washed 3x with fresh PBS+ (1X PBS, 1mM MgCl2, 1mM CaCl 2 , pH 7.4), and then permeabilized with 0.2% Triton X-100 at room temperature for 4 min followed 3 washes with fresh PBS+.…”

Second international symposium on the chaperone code, 2023

“… 56 Gianna Mochi from Mark Woodford’s lab (State University of New York, Upstate Medical University, USA) presented a recently discovered metabolically derived PTM that impacts the function of TRAP1 and its client protein, driving mitochondrial respiration. 57 Siddhi Omkar from the Truman lab (UNC Charlotte, USA) described a screening approach to identify phosphorylation sites that are altered under heat shock and thus studying its cellular rationale that helps cells survive at high temperatures. She identified novel sites on Hsp70 that are modified under heat stress and result in a defective HSR.…”

Mitochondrial Chaperone Code: Just warming up

“…TRAP1 O -GlcNAcylation has been shown to affect the regulation of mitochondrial metabolism. 37 Specifically, OGT-dependent TRAP1 O -GlcNAcylation decreased chaperone function leading to increased mitochondrial respiration. It was further demonstrated that the global effect of O -GlcNAcylation on mitochondrial respiration occurred in a TRAP1-dependent manner.…”