RUBEN K. DAGDA, Ph.D.
Ph.D., University of Iowa, 2006
Location: Manville 19A
Tel: (775) 784-4121
Fax: (775) 784-1620
Persistent dephosphorylation mediated by mitochondrial localized protein phosphatase 2A accelerates neurodegeneration, fragments mitochondria and impairs mitochondrial function. On the other hand, mitochondrial serine/threonine kinases, PTEN induced kinase 1 (PINK1) and mitochondrial PKA confer neuroprotection and regulate overlapping mitochondrial functions including mitochondrial morphology and bioenergetics.
Neurons rely on functionally efficient mitochondria to power critical neuronal functions. Given that impaired mitochondrial turnover and dysfunction underlie the etiology of many neurodegenerative diseases, understanding how reversible phosphorylation at the mitochondria regulates mitochondrial function and turnover will lay the basic groundwork for developing future “mitoprotective” therapies for reversing mitochondrial dysfunction and neurodegeneration. We have previously found that PINK1 and mitochondrial PKA converge at the outer mitochondrial membrane to regulate mitochondrial function and survival.
We are examining how mitochondrial PKA and PINK1 interact at the mitochondria to modulate mitochondrial function, calcium signaling, and survival.
A second area of interest employing proteomics and biochemical approaches in neurons is to determine how mitochondrial turnover (mitophagy) is regulated by mitochondrial PKA and phosphatases by reversibly phosphorylating specific components of the “mitophagosome” complex. A final goal of this project is to synthesize functionalized nanoreagents that can activate prosurvival signaling pathways at the mitochondria as an alternative therapy for reversing mitochondrial pathology induced by neurodegenerative diseases and by normal brain aging.
View the publications of Dr. Dagda on PubMed