TNF-α impairs platelet function by inhibiting autophagy and disrupting metabolism via syntaxin 17 downregulation.

ABSTRACT: Platelets play a dual role in hemostasis and inflammation-associated thrombosis and hemorrhage. Although the mechanisms linking inflammation to platelet dysfunction remain poorly understood, our previous work demonstrated that TNF-α alters mitochondrial mass, platelet activation, and autophagy-related pathways in megakaryocytes. Here, we hypothesized that TNF-α impairs platelet function by disrupting autophagy, a process critical for mitochondrial health and cellular metabolism. Using human and murine models of TNF-α-driven diseases, including myeloproliferative neoplasms and rheumatoid arthritis, we found that TNF-α downregulates syntaxin 17 (STX17), a key mediator of autophagosome-lysosome fusion. This disruption inhibited autophagy, leading to the accumulation of dysfunctional mitochond

SUBMITTER: Rojas-Sanchez G 

PROVIDER: S-EPMC12321402 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature