Site-specific ubiquitination of VDAC1 restricts its oligomerization and mitochondrial DNA release in liver fibrosis

Experimental & Molecular Medicine, Published online: 19 January 2023; doi:10.1038/s12276-022-00923-9The molecular mechanisms causing liver fibrosis, the tissue scarring associated with long-term liver disease, involve an enzyme called Parkin, suggesting that drugs enhancing Parkin activity might delay, reduce or prevent fibrosis. Researchers in China led by Jun Ren and Yingmei Zhang at Fudan University, Shanghai, studied cells from human and mouse liver to investigate the release of DNA from cell organelles called mitochondria, a key feature in the development of liver fibrosis. This DNA release triggers the abnormal immune activity implicated in causing fibrosis. The researchers uncovered a molecular interaction allowing Parkin to restrict the release of DNA from mitochondria. Parkin achieves this effect by modifying a protein channel in the mitochondrial membrane. Enhancing this enzyme’s protective ability could be explored in search of new therapeutic approaches.

Source: Experimental and Molecular Medicine - January 19, 2023 Category: Molecular Biology Authors: Ne N. Wu Lifeng Wang Lu Wang Xihui Xu Gary D. Lopaschuk Yingmei Zhang Jun Ren Source Type: research