ER Stress-Induced Sphingosine-1-Phosphate Lyase Phosphorylation Potentiates the Mitochondrial Unfolded Protein Response

Interaction of PINK1 with nucleotides and kinetin

“…Mutation of the gatekeeper to the smaller residue such as Ala and Gly enables KTP to bind and activate PINK1. These results are consistent with numerous reports of kinases that require a gatekeeper mutation to use KTP (and KTP analogs such as KTPγS) as their phosphate source ( 34 – 39 ). A proteome-wide, mass-spectrometry based study identified 26 putative KTP-binding kinases out of the 218 detected kinases in cell lysates ( 40 ).…”

Exploring the IRE1 interactome: From canonical signaling functions to unexpected roles

“…This links IRE1 with the NF-κB pathway, involved in many cellular processes such as inflammation or apoptosis. At last, the sphingosine 1-phosphate lyase (SPL) was shown to be phosphorylated by IRE1, inhibiting its enzymatic activity and resulting in activation of a mitochondrial-dependent UPR ( 153 ). Even though the experiments performed were mostly in vitro , these discoveries open a new field in the exploration of IRE1 kinase–dependent signaling and raise questions about potential implication of IRE1 in processes not limited to the UPR.…”

Geranylgeranoic acid, a bioactive and endogenous fatty acid in mammals: a review

“…UPR ER induced by PA metabolites such as lyso-PLs and DAGs activates IRE1, followed by enhanced ceramide synthesis and secretion of ceramide-containing extracellular vesicles, which in turn activate TLR4 ( 83 ). In this regard, the recent identification of sphingosine-1-phosphate lyase (SPL) as a substrate of the IRE1 enzyme ( 84 ) points to the possibility that phosphorylation of SPL by IRE1 inhibits its activity, resulting in ceramide increase and consequent activation of TLR4.…”