Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation.

ABSTRACT:

Background and aims

TGF-β induces multiple structural and functional changes in quiescent HSCs, including an increase in proliferation, mitochondrial mass, and matrix deposition. HSC transdifferentiation requires significant bioenergetic capacity, and it is not known how TGF-β-mediated transcriptional upregulation is coordinated with the bioenergetic capacity of HSCs.

Approach and results

Mitochondria are key bioenergetic organelles, and here, we report that TGF-β induces release of mitochondrial DNA (mtDNA) from healthy HSCs through voltage-dependent anion channels (VDACs), with the formation of an mtDNA-CAP on the external mitochondrial membrane. This stimulates organization of cytosolic cyclic GMP-AMP synthase (cGAS) onto the mtDNA-CAP and subsequent activation of the cGA

SUBMITTER: Arumugam S 

PROVIDER: S-EPMC10804318 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature