Reprogramming of lipid metabolism by PFKL promotes the adaptation of pancreatic ductal adenocarcinoma to glucose deprivation.

Authors

Lu Chai, Zhaoyuan Meng, Zhimin Lu, Jing Fang

Published in

Cellular signalling. Pages 112839. Aug 22, 2026. Epub Aug 22, 2026.

Abstract

Lipid droplet (LD)-mitochondria tethering is essential for fatty acid oxidation (FAO), which sustains tumor cell survival under nutrient-deprivation conditions. However, how LD-mitochondria contact is regulated in pancreatic ductal adenocarcinoma (PDAC) is unclear.
This study investigated the signaling pathway that regulates lipid droplet-mitochondria interaction in PDAC under conditions of glucose deprivation, utilizing molecular interaction assays, cellular functional experiments, and clinical sample validation.
Glucose deprivation activated p38, leading to phosphorylation of phosphofructokinase, liver type (PFKL) at T331, which in turn phosphorylated the LD protein perilipin 2 (PLIN2) at S159 in PDAC cells. This enhanced the binding of PLIN2 to mitochondrial protein carnitine palmitoyltransferase-1 A (CPT1A), thereby promoting LD-mitochondria tethering. Disruption of this axis impaired LD-mitochondria contact, reduced lipid consumption and ATP production, decreased cell viability, increased apoptosis, and suppressed tumor growth. In human PDAC samples, phosphorylation levels at both PFKL T331 and PLIN2 S159 were elevated and showed a positive correlation.
PFKL plays a key role in coordinating LD-mitochondria tethering under glucose deprivation in PDAC, and targeting the p38-PFKL-PLIN2-CPT1A axis may represent a promising therapeutic strategy.

PMID:
42632532
Bibliographic data and abstract were imported from PubMed on 23 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.