Superfund Research Program

Multiscale Imaging and Proteomics Core

Project Leader: Mark H. Ellisman
Co-Investigators: Elizabeth A. Komives, Roger Y. Tsien
Grant Number: P42ES010337
Funding Period: 2005-2017

Project-Specific Links

Final Progress Reports

Year:   2016  2009 

The collaboration between University of California-San Diego’s Superfund researchers and those in the Multiscale Imaging and Proteomics Core facilitated the discovery of a role for mitochondrial quality control regulated by Ubc13 in carbon tetrachloride (CCl4; 47th on the 2007 CERCLA priority list) induced liver injury and fibrosis. In the liver, CCl4 induces downregulation of mitochondrial proteins and suppresses mitochondrial function leading to cellular stress. In water or soil, CCl4 contamination is over 1,000 parts per billion at 26% of Superfund sites. Ubc13 is translocated into mitochondria in response to CCl4. The role of Ubc13 in the health of mitochondria is being teased out by UCSD SRP researchers. Ubc13 expression is decreased in advanced fatty liver disease. In liver cells, Ubc13 deficiency reduces mitochondrial biogenesis, causes dysfunction of mitochondrial respiration, mitochondrial fusion impairment, reduction of mitochondrial protein expression, and mitophagy defects. In contrast, Ubc13 is involved in DNA damage repair and appears to act as an E2 conjugating enzyme to participate in ubiquitination of mitochondrial proteins, which process regulates mitophagy and mitochondrial quality, protecting against liver damage induced by toxin exposure. This breakthrough study reveals the mitochondrial-centric mechanism by which Ubc13 is protective against CCl4-induced liver injury and cancer.