A Northwestern Medicine examine opens a brand new avenue of analysis in neurodegenerative issues, by highlighting the significance of direct communication and collaboration between mobile organelles within the pathogenesis of those issues.
Restoring contacts between mitochondria and lysosomes improves neuronal operate.
- Contacts between lysosomes and mitochondria are damaged as a result of Parkinson’s mutation
- Lysosomes can’t ‘feed’ mitochondria with important metabolites
Northwestern Medicine scientists have uncovered a brand new mechanism by which mutations in a gene parkin contribute to familial types of Parkinson’s illness. The discovery opens a brand new avenue for Parkinson’s therapeutics, scientists report in a brand new examine.
Cellular Dysfunction in Parkinson’s
The Northwestern scientists found that mutations in parkin lead to a breakdown of contacts between two key staff within the cell – lysosomes and mitochondria.
Mitochondria are the primary producers of power in cells, and lysosomes recycle mobile particles that accumulates throughout regular operate of our cells. These organelles are particularly necessary in our brains as a result of neurons are extremely depending on power manufacturing by mitochondria, and due to their exercise, neurons produce an abundance of mobile particles that should be cleared by lysosomes.
In a previous examine, revealed in Nature, Dr. Dimitri Krainc, chair of neurology and director of Simpson Querrey Center for Neurogenetics at Northwestern University Feinberg School of Medicine, and his group discovered that lysosomes and mitochondria form contacts with each other. After the initial discovery, Northwestern scientists tried to understand the function of these contacts in Parkinson’s disease.
Inter-Organelle Communication in Parkinson’s
In the new study published on July 19 in the journal Science Advances, the investigators report that lysosomes help mitochondria by providing key metabolites for their function. Mitochondria must import many of their essential ingredients, but it has not been well-known where some of these metabolites come from. On the other hand, lysosomes serve as recycling factories in cells and, therefore, produce many breakdown products that could be used by other organelles such as mitochondria.
In this work, scientists found that lysosomes provide important amino acids that support the function of mitochondria. However, they also found that in some forms of Parkinson’s disease, lysosomes cannot serve as a “helping hand” to mitochondria because the contacts between the two organelles are disrupted. This results in dysfunctional mitochondria and ultimately degeneration of vulnerable neurons in Parkinson’s disease.
“Findings from this study suggest that dysregulation of mitochondria-lysosome contacts contributes to the Parkinson’s disease pathophysiology,” said Krainc, the study’s corresponding author. “We propose that restoring such mitochondria-lysosome contacts represents an important new therapeutic opportunity for Parkinson’s disease.”
Implications and Future Directions
From a broader perspective, this study opens a new avenue of research in neurodegenerative disorders, by highlighting the importance of direct communication and collaboration between cellular organelles in the pathogenesis of these disorders.
Published in Science Advances, the title of the study is “Parkin regulates amino acid homeostasis at mitochondria-lysosome contact sites in Parkinson’s disease.”
Reference: “Parkin regulates amino acid homeostasis at mitochondria-lysosome contact sites in Parkinson’s disease” by Wesley Peng, Leonie F. Schröder, Pingping Song, Yvette C. Wong and Dimitri Krainc, 19 July 2023, Science Advances.
DOI: 10.1126/sciadv.adh3347
The first author of the study is Dr. Wesley Peng who recently completed the medical scientist training program (MD-PhD) at Northwestern and currently serves as a neurology resident at Mass General Brigham and Harvard Medical School. Other contributors to the study include Leonie Schroder, Pingping Song and Yvette Wong.
The study was supported by the following National Institute on Aging grant AG066333, National Institute of Neurological Disorders and Stroke (NINDS) grants NS109252 and NS122257, all from the National Institutes of Health.
