Genes linked to hereditary Parkinson's disease have been found to play a role in recycling mitochondrial products to generate new mitochondria.
Researchers in California have found that Parkinson's disease-associated genes, PINK1 and Parkin, are crucial in the mitochondrial life cycle. Disruption of this pathway could contribute to neurodegenerative conditions, such as Parkinson's.
'This appears to be a new mitochondrial quality control, recycling system,' said co-first author of the research Dr Huihui Li, from Gladstone Institutes in San Francisco. 'We think we've uncovered a pathway of mitochondrial recycling—which is like salvaging valuable furniture in a house before demolishing it.'
Whilst much is known about mitochondrial recycling in other cell types, the process in neurons – the cells affected in neurodegenerative diseases – is less well understood. However, neurons are known to have very high energy demands and mitochondria are essential to energy supply.
The research team used a novel approach to track neuronal mitochondria over time, by combining time-lapse imaging with powerful microscopy. They tracked individual mitochondria for almost a full day at a time.
They found that Parkin proteins encircled damaged mitochondria to target them for a specific type of degradation known as mitophagy. Mitophagy involves the fusion of mitochondria with another part of the cell to form structures called mitolysosomes.
'Until now, nobody has known what happens next to these mitolysosomes… We were able to visualise these steps at a level that hasn't been done before in any cell type,' said senior author Professor Ken Nakamura.
It was previously thought that mitolysosomes were rapidly broken down into molecules for the cells to reuse. However, the research group found that mitolysosomes persisted in the cell for hours; often being engulfed by healthy mitochondria, or spontaneously bursting to release their contents. Without PINK1 or Parkin proteins this process was unable to occur.
'Our study advances our understanding of how these two key Parkinson's disease proteins degrade and recycle mitochondria' said Professor Nakamura. 'Our future studies will investigate how these pathways contribute to disease and how they can be targeted therapeutically.'
The study was published in the journal Science Advances.
Sources and References
-
Genes mutated in Parkinson's Disease linked to mitochondrial recycling in neurons
-
Longitudinal tracking of neuronal mitochondria delineates PINK1/Parkin-dependent mechanisms of mitochondrial recycling and degradation
-
Recycling a cell's energy centers to ward off Parkinson's disease
-
Study reveals the influence of mitochondria in Parkinson's disease
Leave a Reply
You must be logged in to post a comment.