Unknown

Dataset Information

0

Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence.


ABSTRACT: Mitochondrial dynamics is crucial for the regulation of cell homeostasis. Our recent findings suggest that hepatitis C virus (HCV) promotes Parkin-mediated elimination of damaged mitochondria (mitophagy). Here we show that HCV perturbs mitochondrial dynamics by promoting mitochondrial fission followed by mitophagy, which attenuates HCV-induced apoptosis. HCV infection stimulated expression of dynamin-related protein 1 (Drp1) and its mitochondrial receptor, mitochondrial fission factor. HCV further induced the phosphorylation of Drp1 (Ser616) and caused its subsequent translocation to the mitochondria, followed by mitophagy. Interference of HCV-induced mitochondrial fission and mitophagy by Drp1 silencing suppressed HCV secretion, with a concomitant decrease in cellular glycolysis and ATP levels, as well as enhanced innate immune signaling. More importantly, silencing Drp1 or Parkin caused significant increase in apoptotic signaling, evidenced by increased cytochrome C release from mitochondria, caspase 3 activity, and cleavage of poly(ADP-ribose) polymerase. These results suggest that HCV-induced mitochondrial fission and mitophagy serve to attenuate apoptosis and may contribute to persistent HCV infection.

SUBMITTER: Kim SJ 

PROVIDER: S-EPMC4035934 | BioStudies | 2014-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2013-01-01 | S-EPMC3855539 | BioStudies
2017-01-01 | S-EPMC5626535 | BioStudies
1000-01-01 | S-EPMC5503620 | BioStudies
1000-01-01 | S-EPMC5084273 | BioStudies
2015-01-01 | S-EPMC4522211 | BioStudies
2013-01-01 | S-EPMC3610669 | BioStudies
2010-12-20 | S-JCBD-201007013 | BioStudies
1000-01-01 | S-EPMC5045359 | BioStudies
2019-01-01 | S-EPMC6773839 | BioStudies
2020-01-01 | S-EPMC7150875 | BioStudies