kinase interacting protein (AKIP1) is a key regulator of cardiac stress

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 5; pp. E387 - E396
• Main Authors: Sastri, Mira, Haushalter, Kristofer J, Panneerselvam, Mathivadhani, Chang, Philip, Fridolfsson, Heidi, Finley, J Cameron, Ng, Daniel, Schilling, Jan M, Miyanohara, Atsushi, Day, Michele E, Hakozaki, Hiro, Petrosyan, Susanna, Koller, Antonius, King, Charles C, Darshi, Manjula, Blumenthal, Donald K, Ali, Sameh Saad, Roth, David M, Patel, Hemal H, Taylor, Susan S
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 29-01-2013; National Acad Sciences
• Series: PNAS Plus
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Apoptosis; Apoptosis Inducing Factor - metabolism; Biological Sciences; Blotting, Western; Cell Line, Tumor; Cells, Cultured; Heart - physiology; Heart - physiopathology; HEK293 Cells; HeLa Cells; Humans; Hydrogen Peroxide - pharmacology; In Vitro Techniques; Kinases; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Mitochondria; Mitochondria, Heart - metabolism; Myocardial Reperfusion Injury - physiopathology; Myocardium - cytology; Myocardium - metabolism; Myocytes, Cardiac - cytology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Oxidants - pharmacology; Phosphorylation; PNAS Plus; Protein Binding; Rats; Rats, Sprague-Dawley
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1221670110

Significance Early signaling events leading to protection in the heart under cardiac injury are poorly understood. We identified one such protein, A kinase interacting protein (AKIP1), as a modulator that responds to oxidative stress; up-regulation of AKIP1 showed protection to ischemic injury through enhanced mitochondrial integrity. We show AKIP1 functions as a molecular scaffold via interaction with mitochondrial apoptosis inducing factor and increases protein kinase A activity. These mitochondrial signaling complexes assembled by AKIP1 alter the physiological response of the heart under ischemic stress. Understanding molecular activity and regulation of AKIP1 could lead to novel therapeutic approaches to limit myocardial injury.