Ruben Dagda, Ph.D.

Project 4: Modulation of Mitochondrial Quality Control and Function by Serine/Threonine Kinases and Phosphatases in Neurons

Dr. Dagda at Seahorse

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, neuronal development, and survival.

A second area of interest is to determine how mitochondrial turnover (mitophagy) is regulated by mitochondrial PKA and phosphatases by reversibly phosphorylating specific components of the "mitophagosome" complex by employing proteomics and biochemical approaches in neurons.

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 disease and by normal brain aging.


Project 4 Team

Ruben DagdaRuben K. Dagda, Ph.D.

Project 4 Leader

View Dr. Ruben K. Dagda's Faculty Page


Iain BuxtonIain Buxton, D.Pharm.

Project 4 Mentor

View Dr. Iain Buxton's Faculty Page


Sean M. WardRobert Harvey, Ph.D.

Project 4 Mentor

View Dr. Robert Harvey's Faculty Page