Mitochondria are the power engines of the cell. They produce energy by converting sugar and oxygen into chemical forms of energy. In our brain, nerve cells have extremely long cellular extensions, which connect individual nerve cells with each other by forming synapses. Mitochondria are moved into and strategically positioned within those projections to ensure that these connections are supplied with sufficient energy to allow neuronal communication. Consequently, mitochondrial dysfunction can lead to a number of neurological disorders. Therefore, the mechanisms by which mitochondria are replaced or removed are crucial to ensure neuronal health.
Our research has shown that mitochondria can be loaded with protein blueprints when they embark on the journey into the neuronal extensions. This allows them to have a constant supply of proteins they require for their work, even at remote locations in the nerve cell. A protein named synaptojanin 2 facilitates this supply by binding to mitochondria via an adapter protein and simultaneously associating with certain protein blueprints. One of these blueprints can be used to produce a protein called PINK1, which is important in the detection and removal of damaged mitochondria. However, synaptojanin 2 is also able to interact with and modify lipid membranes within the cell, such as the plasma membrane surrounding the cell or endosomes, which are vesicles formed by invaginations of the plasma membrane. The plasma membrane in neurons contains several receptors necessary for the communication between nerve cells. These receptors react to molecules such as neurotransmitters e.g. by opening a hole that permits the entry of Calcium ions into the cell.
Neuronal connections that receive frequent activity produce more of these receptors, strengthening the synapse and making it easier to re-activate the same connection. This process is thought to enable learning, as it creates positive reinforcement of this connection. Another aspect of memory is the ability to remove weak connections. Neurons that should not associate together can repress their communication by removing the neurotransmitter receptors from the plasma membrane by pulling them to the inside of the cell within endosomes where they cannot react to extrinsic signals. We are now asking: What happens if these endosomes come into contact with synaptojanin 2?
