We investigate local mechanisms governing mitochondrial health in neurons
The large size of neurons provides additional challenges for mitochondrial quality control, as the organelle is transported all over the axonal arbor and needs to function far away from the cell body and the bulk of the protein synthesis machinery. Local translation of mitochondrial proteins may alleviate some of this strain, yet mechanisms for mRNA transport and local protein synthesis have not been described for mitochondrial transcripts. Using mRNA live-imaging we observed mitochondrial localization of transcript encoding PTEN-induced kinase 1 (PINK1), a mitochondrial kinase important for mitophagy and mutated in hereditary forms of Parkinson’s disease. This neuron-specific mechanism ensures the local supply of freshly synthesized PINK1 to axonal mitochondria, allowing the removal of potentially hazardous organelles. Current research is focused on the extent of this mechanism of transport, which may be a fundamentally new paradigm of RNA transport and local mitochondrial biogenesis, allowing alterations of the mitochondrial proteome according to the local signaling environment.
We aim to discover the underlying mechanisms that regulate local translation of mitochondrial proteins and to analyze the adaption of this important organelle in response to neuronal activity. A decline in mitochondrial health is a hallmark of many neurodegenerative disorders and aging, so understanding the molecular mechanisms that govern mitochondrial health and functions in neurons will lead to treatments and therapies that increase the healthy life span in elderly people.