Sending bad mitochondria to the garbage disposal: Insights into PINK1/Parkin mitophagy
Mitochondrial dysfunction is a major contributor to the pathogenesis of Parkinson’s disease. PINK1 and Parkin are proteins mutated in familial Parkinson’s disease, which function to maintain a healthy population of mitochondria. PINK1 and Parkin do this by removing damaged mitochondria through a selective form of garbage disposal termed mitophagy. Removal of damaged mitochondria maintains cellular and organismal health by maintaining mitochondrial energy supply, preventing oxidative stress, and by preventing the release of mitochondrial factors that cause cell death and inflammation. PINK1 and Parkin drive mitophagy by selectively tagging damaged mitochondria to trigger their encapsulation by a double membrane structure called an autophagosome. Autophagosomes deliver damaged mitochondria to lysosomes where they are degraded. Despite the importance of PINK1/Parkin mitophagy, little is known about how autophagosomes are built around damaged mitochondria and how autophagy-related (Atg) proteins function during mitophagy. The mechanisms behind how damaged mitochondria are targeted for mitophagy by PINK1 and Parkin will be discussed, with a focus on the molecular steps that govern autophagosome formation.
Michael's research interests are focused on autophagy pathways and various aspects of mitochondrial biology in health and disease. Michael was awarded his PhD in 2008 from La Trobe University studying the assembly of membrane protein complexes in mitochondria and their defects in energy generation disorders. In 2010, Michael conducted his post-doctoral research studies at the National Institutes of Health (USA) where he worked on mitochondrial dysfunction in Parkinson's disease. His research focused on the Parkinson's disease proteins PINK1 and Parkin and their role in maintaining mitochondrial health via selective autophagy. The work led to Michael receiving the 2013 ASBMB Boomerang Award, and in 2014 he returned to Australia to join the Department of Biochemistry and Molecular Biology at Monash University where he is currently an ARC Future Fellow.