Neuron subtypes have distinct mitochondrial transport in axons and vulnerability to tau in vivo

Abstract Mitochondria are the primary energy producing organelles in eukaryotic cells. Their location is tied to the cell compartment’s energy requirement. Whether mitochondria are actively transported and retain their motility in neuronal axons of adult animals remains debated. Here we show not only a higher fraction of motile axonal mitochondria than currently described, but also marked differences in transport dynamics across neuronal subtypes. We further show that aggregated tau in the Locus Coeruleus (LC), an early pathological hallmark of Alzheimer’s disease, impairs mitochondrial transport along axons, an effect absent in cortical inhibitory and excitatory neurons. Collectively, we demonstrate the abundant and diverse motility of neuronal mitochondria in vivo, and reveal a correlate of LC vulnerability to tau proteinopathy in neurodegenerative diseases.