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 researchand nanomedicine of enormous interest. However, little is known abouttheir sublethal effects on biological systems, especially mitochondrialdamage. Here, by using super-resolution imaging in live cells, wediscovered that GO nanosheets damage mitochondrial membranes in adose-dependent manner in both cancer and healthy cell lines. Furthermore,we observed that GO nanosheets destroy the integrity of mitochondrialcristae. We performed simulations to clarify the mechanisms governingthat behavior and found that GO nanosheets insert into membranes,thereby resulting in membrane "cutting" and that thesize of GO nanosheets is an essential factor of inducing fragmentation.Those results, demonstrating that large GO nanosheets induce mitochondrialdamage, indicate that the assessment and safety profiling of GO-basedbiomedical research tools and products should include the carefulevaluation of their effects on mitochondria.