New insights into mitochondrial dynamics and quality control

Project details:
Mitochondria are key organelles essential for ATP generation, calcium buffering and apoptotic signalling. In brain cells including neurons and astrocytes, mitochondrial trafficking is crucial to match mitochondrial positioning to localised energy and calcium buffering demands. Correct mitochondrial dynamics and quality control systems are essential to maintain a functional mitochondrial network and disruption of these processes has been observed in several neurodegenerative diseases (MacAskill et al., 2010; Devine et al., 2015).

Damaged mitochondria can be selectively targeted by several quality-control systems to facilitate their clearance by mitochondrial autophagy (mitophagy). In primary cells such as neurons and astrocytes the mechanisms of mitochondrial turnover including trafficking and clustering of damaged mitochondria prior to and during mitophagy remain poorly understood. The project will use a combination of well-established biochemical and imaging assays to further investigate key differences between the mitophagic process in rodent primary neurons and astrocytes. In particular we will compare damage induced Parkin translocation, mitochondrial ubiquitination of key substrates and mitochondrial clustering rates in astrocytes. This will be combined with state of the art approaches for imaging mitochondrial astrocyte dynamics in situ in brain slices (Stephen et al., 2015) upon mitochondrial damage.