MPV17 does not control cancer cell proliferation

MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene results in hepato-cerebral mitochondrial DNA depletion syndrome. However, in this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 silencing does not control cancer cell proliferation, despite the fact that we initially observed a reduced proliferation rate in five MPV17-silenced cancer cell lines with two different shRNAs. This reduced proliferation phenotype might be due to off-target effects of shRNA-mediated knockdown. RNA interference has been a quantum leap in the field of functional genomic. This scientific breakthrough is a straightforward approach to monitor the aftermaths of the functional loss of a specific gene. However, one must beware the illusion of control that comes with any new technology and acknowledge the unintended events embedded to it. Our results illustrate the insidiousness of off-target effects and emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-based gene silencing. They also clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results.