Подписывайтесь на нас

Одна из главных задач Life4me+ — предотвращение новых случаев заражения ВИЧ-инфекцией и другими ИППП, гепатитом C и туберкулезом.

Приложение позволяет установить анонимную связь между врачами и ВИЧ-позитивными людьми, дает возможность организовать своевременный прием ваших медикаментов, получать замаскированные напоминания о них.

Назад
15 апреля 2014, 23:00
59

Учеными раскрыт механизм повреждения печени при гепатите C

Учеными раскрыт механизм повреждения печени при гепатите C - изображение 1

Significance

Persistent hepatitis C virus (HCV) infection is associated with mitochondrial liver injury. Mitochondrial quality control is established as a physiological adaptation to mitochondrial injury. This study provides a new insight into how HCV disrupts mitochondrial dynamics and evades apoptosis and innate immunity to sustain persistent viral infection. HCV promoted dynamin-related protein 1-mediated mitochondrial fission, followed by mitophagy. Interference of HCV-induced mitochondrial fission and mitophagy led to the suppression of virus secretion, a decrease in glycolysis and ATP generation, an increase in interferon synthesis, and an increase in apoptotic death of infected cells via enhanced apoptotic signaling. These observations implicate the functional relevance of altered mitochondrial dynamics in the pathogenesis of chronic liver disease associated with HCV infection.

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.