Fig. 1 |. Model summarizing the role of PGAM1 in coordinating glycolysis with autophagy in response to changes in nutrient availability.

PGAM1 is a key enzyme in glycolysis, catalysing conversion of 3PG to 2PG, where it is reported to function as a dimer. Work reported by Zhang et al.⁶ shows that PGAM1 is phosphorylated by ULK1 (Atg1) in response to nutrient deprivation (starvation), which induces its interaction with ATG14 and ATG9 at autophagosomes, where it has a crucial role in recruitment of PI3K complexes, is required for LC3 processing and promotes p62 degradation (all key autophagy functions). This role of PGAM1 in autophagy is accompanied by decreased activity in glycolysis despite the catalytic activity of PGAM1 not being required for its function in autophagy — its role in glycolysis and autophagy are shown to be separable. Thus, it is postulated that PGAM1 levels may be limiting under starvation conditions, and that this favours its role in autophagy. However, both PGAM1 functions (glycolysis and autophagy) are important in cancer and this may explain the selective pressure to upregulate PGAM1 (either via loss of p53 or via increased mTORC1–HIF1α signalling). The overexpression of PGAM1 in cancers may thus allow it to promote both glycolysis and autophagy simultaneously.