Mitochondrial Biogenesis in Neurons: How and Where

Neurons rely mostly on mitochondria for the production of ATP and Ca2+ homeostasis. As sub-compartmentalized cells, they have different pools of mitochondria in each compartment that are maintained by a constant mitochondrial turnover. It is assumed that most mitochondria are generated in the cell body and then travel to the synapse to exert their functions. Once damaged, mitochondria have to travel back to the cell body for degradation. However, in long cells, like motor neurons, this constant travel back and forth is not an energetically favourable process, thus mitochondrial biogenesis must also occur at the periphery. Ca2+ and ATP levels are the main triggers for mitochondrial biogenesis in the cell body, in a mechanism dependent on the Peroxisome-proliferator-activated gamma co-activator-1 alpha-nuclear respiration factors 1 and 2-mitochondrial transcription factor A (PGC-1 alpha-NRF-1/2-TFAM) pathway. However, even though of extreme importance, very little is known about the mechanisms promoting mitochondrial biogenesis away from the cell body. In this review, we bring forward the evoked mechanisms that are at play for mitochondrial biogenesis in the cell body and periphery. Moreover, we postulate that mitochondrial biogenesis may vary locally within the same neuron, and we build upon the hypotheses that, in the periphery, local protein synthesis is responsible for giving all the machinery required for mitochondria to replicate themselves.

Automated summary

Neurons primarily rely on mitochondria for ATP production and Ca2+ homeostasis, with different pools of mitochondria in each sub-compartment. Mitochondria are generated in the cell body and travel to the synapse, but in long cells like motor neurons, biogenesis also occurs at the periphery. Mitochondrial biogenesis in the cell body is triggered by Ca2+ and ATP levels, while mechanisms promoting biogenesis away from the cell body are less understood.