Northwestern Medicine scientists have uncovered a recent mechanism by which mutations in a gene parkin contribute to familial types of Parkinson’s disease. The invention opens a recent avenue for Parkinson’s therapeutics, scientists report in a recent study.

The Northwestern scientists discovered that mutations in parkin lead to a breakdown of contacts between two key employees within the cell –- lysosomes and mitochondria.

Mitochondria are the predominant producers of energy in cells, and lysosomes recycle cellular debris that accumulates during normal function of our cells. These organelles are especially necessary in our brains because neurons are highly depending on energy production by mitochondria, and since of their activity, neurons produce an abundance of cellular debris that have to be cleared by lysosomes.

In a previous study, published 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 one another. After the initial discovery, Northwestern scientists tried to know the function of those contacts in Parkinson’s disease.

In the brand new study published in Science Advances, the investigators report that lysosomes help mitochondria by providing key metabolites for his or her function. Mitochondria must import a lot of their essential ingredients, nevertheless it has not been well-known where a few of these metabolites come from. However, lysosomes function recycling factories in cells and, subsequently, produce many breakdown products that may very well be utilized by other organelles similar to mitochondria.

On this work, scientists found that lysosomes provide necessary amino acids that support the function of mitochondria. Nonetheless, in addition they found that in some types of Parkinson’s disease, lysosomes cannot function a “helping hand” to mitochondria since the contacts between the 2 organelles are disrupted. This ends 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 creator. “We propose that restoring such mitochondria-lysosome contacts represents a crucial recent therapeutic opportunity for Parkinson’s disease.”

From a broader perspective, this study opens a recent avenue of research in neurodegenerative disorders, by highlighting the importance of direct communication and collaboration between cellular organelles within the pathogenesis of those disorders.

The primary creator of the study is Dr. Wesley Peng who recently accomplished 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 title of the study is “Parkin regulates amino acid homeostasis at mitochondria-lysosome contact sites in Parkinson’s disease.”

The study was supported by the next 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.

Source:

Journal reference:

Peng, W., et al. (2023) Parkin regulates amino acid homeostasis at mitochondria-lysosome contact sites in Parkinson’s disease. Science Advances. doi.org/10.1126/sciadv.adh3347.