The role of PKA anchoring and localization in mitochondria

Ken Humphries

Appointment Period: 2000-2001 / Grant Year: [16]

Mitochondria are the major source of energy production within the cell and are therefore essential for both normal cellular homeostasis and growth. The Taylor lab has previously identified two A-kinase anchoring proteins (DAKAP1 and 2) that are localized to the mitochondria and have affinity for both RI and RII types of protein kinase A (PKA) regulatory subunits. Because PKA can phosphorylate a number of substrates upon cellular increase in cAMP levels, it is believed that localization of the kinase proximal to target substrates is necessary to ensure specificity. Identification of AKAP's associated with the mitochondria therefore suggests that PKA may play a role in mitochondrial function by phosphorylating specific organelle components. The goal of my project is determine a functional role of DAKAP's within the mitochondria. Utilizing both isolated mitochondria and intact cells, we examined alterations in mitochondrial respiration, release of cytochrome-c, and changes in electron transport chain activity due to altered PKA signaling.

PUBLICATIONS (resulting from this training, and some recent ones)

Humphries KM, Juliano C, Taylor SS. (2002) Regulation of cAMP-dependent protein kinase activity by glutathionylation. J Biol Chem. 277:43505-11.

Humphries KM, Deal MS, Taylor SS. (2005) Enhanced dephosphorylation of cAMP-dependent protein kinase by oxidation and thiol modification. J Biol Chem. 280:2750-8.

Humphries KM, Szweda PA, Szweda LI. (2006) Aging: a shift from redox regulation to oxidative damage. Free Radic Res. 40:1239-43.