Mitochondrial health maintenance in neurons

Description

Abstract Neurons with their elaborate and extended morphology must employ homeostatic mechanisms that allow neuronal mitochondria to exist far away from the cell body while still retaining a functional proteome. This process, called “Mitostasis”, is most likely a finely tuned concert of mitochondrial transport, local protein synthesis and local degradation by proteasomal and autophagic mechanisms.

However, the processes that allow transport mRNAs encoding for mitochondrial proteins are only partially understood. Using the transcript of PTEN-induced kinase 1 (PINK1) as a model substrate we have discovered that this RNA associates with mitochondria specifically in neurons and uses mitochondria as a means of transport into axons and dendrites. This is a neuron specific mechanism driven by selective expression of an mRNA anchoring complex at the outer mitochondrial membrane. Loss of this complex impairs local PINK1 function in the removal of damaged organelles (mitophagy) and hence mitostasis. Modulation of this pathway may therefore prove beneficial in the treatment of mitostatic diseases including Parkinson’s disease.