How AMPK and PKA Interplay to Regulate Mitochondrial Function and Survival in Models of Ischemia and Diabetes. (17th December 2017)

• Record Type: Journal Article
• Authors: Zhang, Jingdian; Wang, Yumeng; Liu, Xiaofeng; Dagda, Ruben K.; Zhang, Ying
• Other Names: Radziwon-Balicka Aneta Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2017(2017)
• Publication Date: 2017-12-17
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2017/4353510
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Adenosine monophosphate-activated protein kinase (AMPK) is a conserved, redox-activated master regulator of cell metabolism. In the presence of oxidative stress, AMPK promotes cytoprotection by enhancing the conservation of energy by suppressing protein translation and by stimulating autophagy. AMPK interplays with protein kinase A (PKA) to regulate oxidative stress, mitochondrial function, and cell survival. AMPK and dual-specificity A-kinase anchoring protein 1 (D-AKAP1), a mitochondrial-directed scaffold of PKA, interact to regulate mitochondrial function and oxidative stress in cardiac and endothelial cells. Ischemia and diabetes, a chronic disease that increases the onset of cardiovascular diseases, suppress the cardioprotective effects of AMPK and PKA. Here, we review the molecular mechanisms by which AMPK and D-AKAP1/PKA interplay to regulate mitochondrial function, oxidative stress, and signaling pathways that prime endothelial cells, cardiac cells, and neurons for cytoprotection against oxidative stress. We discuss recent literature showing how temporal dynamics and localization of activated AMPK and PKA holoenzymes play a crucial role in governing cellular bioenergetics and cell survival in models of ischemia, cardiovascular diseases, and diabetes. Finally, we propose therapeutic strategies that tout localized PKA and AMPK signaling to reverse mitochondrial dysfunction, oxidative stress, and death of neurons and cardiac and endothelial cells during ischemia and diabetes.