25 Years of PI5P

Abstract

The accidental discovery of PI5P (phosphatidylinositol-5-phosphate) was published 25 years ago, when PIP5K type II (phosphoinositide-4-phosphate 5-kinase) was shown to actually be a 4-kinase that uses PI5P as a substrate to generate PI(4,5)P2. Consequently, PIP5K type II was renamed to PI5P4K, or PIP4K for short, and PI5P became the last of the 7 signaling phosphoinositides to be discovered. Much of what we know about PI5P comes from genetic studies of PIP4K, as the pathways for PI5P synthesis, the downstream targets of PI5P and how PI5P affects cellular function all remain largely enigmatic. Nevertheless, PI5P and PI5P-dependent PI(4,5)P2 synthesis have been clearly implicated in metabolic homeostasis and in diseases such as cancer. Here, we review the past 25 years of PI5P research, with particular emphasis on the impact this small signaling lipid has on human health.

Kinase signalling adaptation supports dysfunctional mitochondria in disease

“…One group of lipids with crucial signalling activity are the phosphatidylinositols (PI), which can be phosphorylated at two positions converting PI to phosphatidylinositol-4,5-bisphosphate (PIP 2 ). The two consecutive phosphorylation events are mediated through the phosphatidylinositol 4-kinases (PI4Ks), the PtdInsP-5-OH kinases (PIP(5)Ks), and the Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) (Whitman et al, 1987;Rameh et al, 1997;Rameh and Blind, 2023). These kinases are grouped into class II and class III.…”