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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Siddiqui, Aleem Kim, Seong-jun Gish, Robert G. Syed, Gulam H. Chiu, Wei-wei Sohail, Muhammad A. Khan, Mohsin |
| Description | Author Affiliation: Kim SJ ( Division of Infectious Diseases and Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla, CA 92093.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 17 |
| Volume Number | 111 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2014-04-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Hepacivirus Physiology Mitochondrial Dynamics Autophagy Cell Line, Tumor Dynamins Metabolism Immune Evasion Immunity, Innate Membrane Proteins Mitochondria Ultrastructure Mitochondrial Degradation Mitochondrial Proteins Phosphorylation Phosphoserine Protein Transport Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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