A significant number of studies have focused on the role of HCV core protein in mitochondrial dysfunction [11, 14, 15, 20, 26, 32] . In this study, cells expressing only the nonstructural proteins were also shown to have suffered from mitochondrial damage, and the extent of damage, in terms of mitochondrial size and number, was comparable to that of cells expressing the full-length polyprotein or core protein (Figures 2A  and 2B ). In addition, the level of ROS production in the mitochondria, as detected by MitoSOX, was also comparable among the three HCV protein-expressing cell lines after adjusting for total mitochondria (Figures 2C and 2D) . The data suggest that multiple HCV proteins are capable of entering the mitochondria and cause increased oxidative stress, although the underlying mechanism may not be the same for each protein. The core protein-expressing cells had the lowest number of mitochondria per cell ( Figure 2B ). The data implies that Core-on cells may suffer from the most severe mitochondrial loss among the three HCV protein-expressing cell lines. Whether this is due to the higher level of core protein expression in Core-on cells ( Figure S1A ) will need to be examined with other approaches.