Mitochondria are absent from microglial processes performing surveillance, chemotaxis, and phagocytic engulfment.

Microglia continually surveil the brain allowing for rapid detection of tissue damage or infection. Microglial metabolism is linked to tissue homeostasis, yet how mitochondria are subcellularly partitioned in microglia and dynamically reorganize during surveillance, injury responses, and phagocytic engulfment in the intact brain are not known. Here, we performed intravital imaging and ultrastructural analyses of microglia mitochondria in mice and human tissue, revealing that microglial processes diverge in their mitochondrial content, with some containing multiple mitochondria while others are completely void. Microtubules and hexokinase 2 mirror this uneven mitochondrial distribution indicating that these cytoskeletal and metabolic components are linked to mitochondrial organization in microglia. Microglial processes that engage in minute-to-minute surveillance typically do not have mitochondria. Moreover, unlike process surveillance, mitochondrial motility does not change with animal anesthesia. Likewise, the processes that acutely chemoattract to a lesion site or initially engage with a neuron undergoing programmed cell death do not contain mitochondria. Rather, microglia mitochondria have a delayed arrival into the responding cell processes. Thus, there is subcellular heterogeneity of mitochondrial partitioning. Moreover, microglial processes that surveil and acutely respond to damage do not contain mitochondria.