Table of Contents
What does ULK1 stand for?
Unc-51 like autophagy activating kinase (ULK1/2) are two similar isoforms of an enzyme that in humans are encoded by the ULK1/2 genes. It is specifically a kinase that is involved with autophagy, particularly in response to amino acid withdrawal.
What is the function of ULK1?
ULK1 in bulk and selective autophagy initiation ULK1 is integral in initiating autophagy in response to various signals. The initiation of bulk autophagy is inhibited when ULK1 and ATG13 are phosphorylated by mTORC1. ULK1 phosphorylates the PI3KC3 complex subunit BECN1 and activates PI3KC3.
What activates ULK1?
The study by Guan and colleagues48 suggests that phosphorylation of AMPK sites on ULK1 is stimulated by glucose starvation, contributing to ULK1 activation. In this case, ULK1 kinase activity (measured by ULK1 autophosphorylation) increases upon glucose starvation, and is correlated with AMPK activation.
Does mitophagy lead to autophagy?
Mitophagy Control As mitophagy requires autophagosome sequestration, several feedback mechanisms link to autophagy initiation. BECN1 is involved with mitochondrial translocation of PRKN, where it colocalizes with PINK1 and PRKN at MAMs (39, 74).
How is ULK1 activated?
The ULK1 complex drives formation of the phagophore, the initial autophagosomal precursor membrane structure, through direct activation of the VPS34 (vacuolar protein sorting 34) complex and by mediating trafficking of ATG (autophagy-related protein) 9 (ATG9).
How does ULK1 activate autophagy?
ULK1 senses upstream signals from mTOR or AMPK, which can lead to prevention or activation of the downstream autophagy pathway. PKC inhibits autophagy by directly phosphorylating the central conjugation system protein LC3. We speculated that PKC may phosphorylate other autophagy-related proteins to regulate autophagy.
What is the function of Atg1?
Atg1 is the sole protein kinase among the Atg proteins, and it is this kinase activity, enhanced by autophosphorylation during nutrient starvation, that is essential for autophagosome formation (Kamada et al., 2000; Cheong et al., 2008; Yeh et al., 2011 ).
Where are Atg1 and Atg13 recruited during autophagy?
At the onset of autophagy, Atg1 and its positive regulator Atg13 are recruited to the phagophore assembly site (PAS), where they are thought to nucleate the formation of autophagosomal structures.
What is the function of Ser/Thr kinase ATG1 in Saccharomyces cerevisiae?
In S. cerevisiae, the Ser/Thr kinase Atg1 and its major regulators Atg13 and Atg17 control IM initiation (Figure 4.1B ). The Atg1 complex is tonically inhibited by target of rapamycin (TOR) signaling, which prevents autophagosome formation in the presence of nutrients (reviewed in Mizushima et al., 2011 ).
How does Atg1 inhibit S6K?
Moreover, we demonstrated that ATG1 specifically inhibits S6K activity by blocking phosphorylation of S6K at Thr 389. Taken together, our genetic and biochemical results strongly indicate crosstalk between autophagy and cell growth regulation.