Unraveling the interplay of glycolysis, lactylation, and autophagy

Glycolysis and macroautophagy (hereafter autophagy) are fundamental biological processes involved in many physiological and pathological settings. Both have been shown to play pivotal roles in tumor initiation and progression. Metabolic reprogramming has been proposed as one of the hallmarks of cancer although in recent times the role of oxidative metabolism in tumorigenesis has been reevaluated and it seems more appropriate to talk about upregulated glycolytic or oxidative metabolism. Autophagy on the other hand, has been shown to play an antitumor role in initial stages of tumorigenesis, while having a tumor-promoting role in tumor progression. Glycolysis and autophagy have long been known to have a complex relationship with each other. In this article we give a picture of this relationship. We show that glycolysis can promote either upregulation or inhibition of autophagy. Vice versa, autophagy can also either promote upregulation or inhibition of glycolytic metabolism. These are highly contradictory effects that appear difficult to reconcile. We suggest that induction of glycolysis or autophagy in the presence of nutrient deprivation or nutrient sufficiency may be at the origin of at least part of these contradictory findings.