Graphene Oxide Nanosheets Induce Mitochondrial Fragmentation by Cutting through Membrane

Graphene oxide (GO)-based nanomaterials have unique physical, chemical, and biological properties that make their use in biomedical research and nanomedicine of enormous interest. However, little is known about their sublethal effects on biological systems, especially mitochondrial damage. Here, by using super-resolution imaging in live cells, we discovered that GO nanosheets damage mitochondrial membranes in a dose-dependent manner in both cancer and healthy cell lines. Furthermore, we observed that GO nanosheets destroy the integrity of mitochondrial cristae. We performed simulations to clarify the mechanisms governing that behavior and found that GO nanosheets insert into membranes, thereby resulting in membrane "cutting" and that the size of GO nanosheets is an essential factor of inducing fragmentation. Those results, demonstrating that large GO nanosheets induce mitochondrial damage, indicate that the assessment and safety profiling of GO-based biomedical research tools and products should include the careful evaluation of their effects on mitochondria.