MPV17 does not control cancer cell proliferation

Morgane Canonne,Patricia Renard,Etienne Sokal,Thierry Arnould,Antoine Fattaccioli,Thuy Truong An Nguyen,Alexis Khelfi,Mustapha Najimi,Sophie Ayama-Canden,Martine Van Steenbrugge,Anaïs Wanet,Negin P Martin

doi:10.1371/journal.pone.0229834

Abstract

MPV17 is described as a mitochondrial inner membrane channel. Although its function remains elusive, mutations in the MPV17 gene result in hepato-cerebral mitochondrial DNA depletion syndrome in humans. In this study, we show that MPV17 silencing does not induce depletion in mitochondrial DNA content in cancer cells. We also show that MPV17 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. However, shRNA-mediated MPV17 knockdown performed in this work provided misguiding results regarding the resulting proliferation phenotype and only a rescue experiment was able to shed definitive light on the implication of MPV17 in cancer cell proliferation. Our results therefore emphasize the caution that is required when scientific conclusions are drawn from a work based on lentiviral vector-based gene silencing and clearly demonstrate the need to systematically perform a rescue experiment in order to ascertain the specific nature of the experimental results.

Highlights

MPV17 is a functionally elusive protein localized in the inner membrane of mitochondrion and for which the encoding gene is located on chromosome 2p23-21 [1] [2] [3] [4]
Taking advantage of The Genome Cancer Atlas (TGCA) database, we show that the abundance of MPV17 transcript is significantly higher in tumours of 10 different tissues, including liver, bile duct, and colon (Fig 1A)
In this work we studied the putative role of MPV17 in cancer cell proliferation

Summary

Introduction

MPV17 is a functionally elusive protein localized in the inner membrane of mitochondrion and for which the encoding gene is located on chromosome 2p23-21 [1] [2] [3] [4]. MPV17 loss-of-function causes a rare autosomal recessive mitochondrial disorder called Mitochondrial DNA Depletion Syndrome (MDDS) marked by a highly reduced mitochondrial DNA (mtDNA) copy number in affected tissues. The vast majority of these patients (96%) suffer from the hepato-cerebral form of MDDS and exhibit a severe mtDNA depletion in the liver (60–99% reduction). This is correlated with a decreased activity of respiratory chain complexes. The onset of the disease takes place early in life (neonatal period/ infancy) and condemn the affected individual to a premature death due to liver dysfunction progressing into liver failure. The remaining 4% of the patients suffer from a late-onset encephalomyopathic disease with mild or no liver involvement [5]

Methods

Results

Conclusion