24Observing large-scale three-dimensional (3D) subcellular dynamics in vivo at high 1 spatiotemporal resolution has long been a pursuit for biology. However, both the 2 signal-to-noise ratio and resolution degradation in multicellular organisms pose 3 great challenges. Here, we propose a method, termed Digital Adaptive Optics 4 Scanning Lightfield Mutual Iterative Tomography (DAOSLIMIT), featuring both 5 3D incoherent synthetic aperture and tiled wavefront correction in post-processing. 6 We achieve aberration-free fluorescence imaging in vivo over a 150 × 150 × 16 µm 3 7 field-of-view with the spatiotemporal resolution up to 250 nm laterally and 320 nm 8 axially at 100 Hz, corresponding to a huge data throughput of over 15 Giga-voxels 9 per second. Various fast subcellular processes are observed, including 10 mitochondrial dynamics in cultured neurons, membrane dynamics in zebrafish 11 embryos, and calcium propagation in cardiac cells, human cerebral organoids, and 12 Drosophila larval neurons, enabling simultaneous in vivo studies of morphological 13 and functional dynamics in 3D. 14 Cells in living organs compose an exquisite microscopic world in which the logistics, 15plasticity, interaction, and migration of multiple subcellular organelles can only be 16 appreciated with high spatiotemporal resolution 1,2 . However, current microscopy 17 techniques only image a certain plane at one time, with three-dimensional (3D) imaging 18 obtained through movements of the focal plane relative to the specimen, such as 19 confocal 3,4 , structured illumination 5,6 , light sheet microscopy 7-9 , etc. A few emerging 20 imaging techniques 10 aiming at simultaneous 3D imaging have been developed recently, 21 such as light field microscopy (LFM) 11,12 , multi-focus microscopy 13,14 , etc. Although 22 LFM has achieved great success in high-speed large-scale 3D calcium imaging 12,15,16 with 23 single-cell resolution, its resolution is typically limited to ~1 µm by the intrinsic trade-off 24 between spatial and angular precision 17,18 , which is barely enough for subcellular 25 structures. With holographic gratings, multi-focus images can be detected simultaneously 26 at different areas on a large CCD camera 13,19 . However, they can only collect several