This is so cool!! Idk if this is a stupid question given that I know literally nothing about sample prep methods for cryo-EM, but how difficult would it be to do this kind of imaging on mitos isolated from mammalian tissues?

If you want to do it on isolated mito from mammalian tissues (which is not what we've done here, no isolation in our case!) it was already done ! You can check here www.nature.com/articles/s41... But it's still very challenging!

High-resolution in situ structures of mammalian respiratory supercomplexes - Nature

Mammalian respiratory supercomplexes are imaged in their native membrane environment by in situ cryo-electron microscopy, providing insight into their reactive intermediates and conformational dynamic...