MITOCHONDRIAL TRANSFER: RECONFIGURING ASTROCYTE METABOLISM

Astrocytes are essential for maintaining metabolic balance and supporting neuronal function in the central nervous system, a role sustained via continuous and intimate communication with neurons. Within this dialogue, the intercellular exchange of mitochondria has recently gained attention as a mechanism influencing mitochondrial composition and performance. Nevertheless, the extent to which this process contributes to metabolic remodeling remains largely unexplored.
In this study, we report a physiological exchange of mitochondria between neurons and glial cells in vivo, that is differentially regulated across brain regions and neuronal subtypes. This process is underpinned by mitochondrial dynamics and transport, enabling astrocytes to incorporate mitochondria that may be either functional or impaired. These organelles are subsequently sorted for integration or degradation, coinciding with coordinated changes in astrocyte morphology and function. Importantly, a substantial subset of astrocytes internalizes neuronal mitochondria to reshape their metabolic state, bioenergetic capacity, and oxygen consumption; surprisingly, mitochondrial respiration can be diminished despite the uptake of exogenous mitochondria. These metabolic shifts are accompanied by transcriptional responses that drive extensive reprogramming of astrocyte physiology.
Collectively, our findings demonstrate that mitochondrial uptake by astrocytes profoundly alters their metabolic and signaling properties, suggesting important consequences for neuron–glia communication under both physiological and pathological conditions.