Spotlight on cellular power plants

Angelika Harbauer receives ERC Starting Grant for her research on mitochondria

Many neurological disorders are associated with dysfunctions in cellular power plants, the mitochondria. Angelika Harbauer and her team at the MPI for Biological Intelligence (in foundation) study mitochondria in nerve cells to better understand the development of disease and the mode of action of pharmaceuticals. Among other things, the scientists want to know how cellular communication pathways influence the production and function of mitochondria. This research will now be supported by a Starting Grant from the European Research Council (ERC) of € 1.5 million for the next five years.

Mitochondria are part of the "critical infrastructure" of our cells – they provide most of the energy our cells need to function. In neurons, mitochondria are particularly busy, since the transmission of information along the cells' long projections requires a lot of energy. Consequently, mitochondrial dysfunction can lead to a number of neurological disorders. These include neurodegenerative diseases such as Alzheimer's, and neuropsychiatric diseases such as bipolar disorders.

Angelika Harbauer investigates how mitochondria are formed in neurons, how they function, and how they are recycled when they malfunction. In their latest study, Angelika Harbauer’s team and colleagues in the USA showed that mitochondria take along protein blueprints on their journey through the neuron. In this way, mitochondria ensure a constant supply of proteins they require for their work, even at remote locations in the nerve cell.

One of the proteins important to mitochondria is synaptojanin 2. It modulates cellular signaling, helps mitochondria to transport protein blueprints, and is involved in mitochondrial quality control. "However, we don't know yet how exactly this protein affects mitochondria," says group leader Angelika Harbauer. "How do synaptojanin 2 and related proteins influence the production, function, and recycling of mitochondria? And what is the role of cellular communication signals in this process?"

In her new project, now funded by the ERC, Angelika Harbauer aims to explore the relationship between mitochondria and synaptojanin 2 in detail. Mitochondria exchange information with other cell components via biochemical signals – this allows our cells to control mitochondrial activity. In many diseases, these communication signals are disrupted. Some of the drugs that are used to treat neurological disorders act through a communication pathway that also involves synaptojanin 2, which in turn is in touch with mitochondria. "We hope to better understand how cellular signaling pathways and drugs affect synaptojanin 2 and mitochondrial function. This may also provide us with starting points for new therapies," explains Angelika Harbauer.

Angelika Harbauer's research group will work closely with the teams of Jörgen Kornfeld and Rüdiger Klein at the institute as part of their new project. "The ERC Starting Grant will enable us to make optimal use of existing synergies," says Angelika Harbauer. "Together, we aim to follow the path from the molecular mechanisms in individual cells to their influence on behavior. Only when we understand the fundamental relationships, we can think about therapeutic targets."