Mitochondrial proteostasis in axons: key roles for neuronal health

Abstract Neurons integrate perception, motor, and cognitive functions, relying heavily on mitochondria for ATP production to support axonal transport, synaptic activity, and maintenance of membrane potential. Mitochondrial dysfunction disrupts energy supply, increases oxidative stress, and impairs calcium buffering, contributing to axonal degeneration in neurodegenerative diseases. Mitochondria are strategically located and transported within highly polarised neurons, posing the problem of maintaining functional organelles in axonal and dendritic regions far away from the cell body. This article highlights mechanisms that ensure the quality of the mitochondrial proteome in neurons.