Abstract / Summary
As a lactate-derived post-translational modification, lactylation plays a vital role in connecting cellular glycolysis with the regulation of cuproptosis, a unique form of cell death triggered by copper overload. The article explores the growing relationship between lactylation and cuproptosis, highlighting the potential for lactate metabolism to influence cellular responses to copper toxicity. We further discuss the potential roles of lactylation writers, erasers and readers in modulating key cuproptosis-related proteins, such as FDX1, DLAT and CTR1, through the specific actions of molecular players including METTL16, NAT10, and NUDT21 across transcriptional regulation, alternative polyadenylation (APA), and m6A modification pathways. Further analysis of the lactate paradox involves exploring the roles lactate plays in various tumor microenvironments and disease contexts. Clinically, this proposed metabolic-epigenetic interplay could be targeted with lactate metabolism inhibitors or copper ionophores to potentially provide synergistic therapeutic strategies for cancer and metabolic diseases. This metabolic–epigenetic interplay could shed light on disease progression and open up new possibilities for precision medical approaches.