Max Delbrueck Center for Molecular Medicine (MDC) 1 article published in JoVE Neuroscience Generation of Human Brain Organoids for Mitochondrial Disease Modeling Stephanie Le1, Laura Petersilie2, Gizem Inak1,4, Carmen Menacho-Pando1, Karl W. Kafitz2, Agnieszka Rybak-Wolf3, Nikolaus Rajewsky3, Christine R. Rose2, Alessandro Prigione1,5 1Department of General Pediatrics, Neonatology and Pediatric Cardiology, Duesseldorf University Hospital, Medical Faculty, Heinrich Heine University, 2Institute of Neurobiology, Heinrich Heine University, 3Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrueck Center for Molecular Medicine (MDC), 4Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, 5Max Delbrueck Center for Molecular Medicine (MDC) We describe a detailed protocol for the generation of human induced pluripotent stem cell-derived brain organoids and their use in modeling mitochondrial diseases.