Mitochondria are often pigeon-holed as the "powerhouse of the cell", giving the false impression that their primary role is as an ATP generator passively responding to the energetic demands of their environment. This is far from the truth. The mitochondria exist as a dynamic network that senses, integrates, and transduces biochemical, energetic, and physical signals, and these signals shape cell fate, lifespan, cancer risk, and more. This session explores emerging tools and methods to edit the small, maternally-inherited, circular mitochondrial genome present in dozens-to-hundreds of copies per cell as a means to prevent mitochondrial disease and optimize metabolic fitness. Additionally, we will discuss the promise of mitochondrial transplantation methodologies as a therapeutic intervention and to discuss the possible routes for mitochondrial metabolic engineering and a range of synthetic developments.