Spatial and morphological organization of mitochondria across a connectome

Abstract

Neuronal function depends critically on the cell biological organization of mitochondria, which regulate calcium signals and produce energy, among other roles. However, little is known about how mitochondria are organized within the circuits of neurons that make up each brain. To uncover the systematic rules that govern mitochondria shape and position in a connectome, we analyzed the morphological and spatial organization of more than 100,000 mitochondria in over 1,000 visual projection neurons in the Drosophila connectome. We found that mitochondrial shape and size differ systematically between cell types, and are distinct enough between cell types to serve as an identifying fingerprint. Moreover, we derived three quantitative rules that describe how mitochondria are positioned within neurons relative to synapses and other subcellular features: (1) they are positioned with a precision of 2-3 microns; (2) their relative preference for pre- and postsynaptic sites and other subcellular features differs between axons and dendrites; (3) their positions were specialized to different cell types. These organizing rules correlated with functional and anatomical properties of the cells, including visual responses and input connectivity. We also find that, in the flys olfactory associative learning circuits, mitochondria are enriched at presynapses to particular postsynaptic cells by accumulating in functional sub-compartments of axons. Overall, our findings reveal a robust set of organizing principles for mitochondria within and between cells, uncovering cell biology that maps onto the organization of the connectome and adding new dimensions for understanding circuit function in the connectome.