ECHS1 K115 succinylation inhibits fatty acid β-oxidation in pancreatic ductal adenocarcinoma.

Downregulated ECHS1 K115 succinylation (K115su) in pancreatic cancer is linked to reduced fatty acid β-oxidation (FAO) activity.

• Why it matters: Metabolic reprogramming in pancreatic ductal adenocarcinoma (PDAC) is shaped by acylation changes, but which succinylation sites regulate FAO remained unclear.
• What they did: The team performed a comprehensive succinylproteome analysis on a prospectively collected PDAC cohort, then integrated succinylome data with lysine lactylation cross-talk to pinpoint FAO-related Ksu sites, including ECHS1 K115su.
• The result: They verified that K115su lowers ECHS1’s conversion of its substrate, inhibiting FAO metabolism, and thereby implicating ECHS1 K115su in PDAC progression.

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