AKAP350C targets to mitochondria via a novel amphipathic alpha helical domain

Abstract

Mitochondria regulate metabolism and homeostasis within cells. Mitochondria are also very dynamic organelles, constantly undergoing fission and fusion. The importance of maintaining proper mitochondrial dynamics is evident in the various diseases associated with defects in these processes. Protein kinase A (PKA) is a key regulator of mitochondrial dynamics. PKA is spatially regulated by A-Kinase Anchoring Proteins (AKAPs). We completed cloning of a novel AKAP350 isoform, AKAP350C. Immunostaining for endogenous AKAP350C showed localization to mitochondria. The carboxyl-terminal 54-amino acid sequence unique to AKAP350C contains a novel amphipathic alpha helical mitochondrial-targeting domain. AKAP350C co-localizes with Mff (mitochondrial fission protein) and mitofusins 1 and 2 (mitochondrial fusion proteins), and likely regulates mitochondrial dynamics by scaffolding PKA and mitochondrial fission and fusion proteins.

Keywords:

• AKAP
• AKAP350
• AKAP9
• CG-NAP
• AKAP450
• mitochondria
• mitofusin
• Mff

Abbreviations:

• AKAP350, A-kinase anchoring protein 350
• Mff, Mitochondrial fission protein
• Mfn1, Mitofusin 1
• Mfn2, Mitofusin 2

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Additional information

Funding

This work was supported by the NIH grant R01 DK043405 to J.R.G. Confocal fluorescence microscopy was performed through the use of the VUMC Cell Imaging Shared Resource supported by National Institute of Health (NIH) Grants CA68485, DK20593, DK58404 and HD15052.