Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 38, Issue 1, Pages 2-11Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2004.09.030
Keywords
mitochondria; protein kinases; programmed cell death; protein trafficking/translocation; scaffold proteins; oxidative stress; Parkinson's/Lewy body disease; cancer; free radical
Funding
- NINDS NIH HHS [R01 NS040817-02, R01 NS040817-03, R01 NS40817] Funding Source: Medline
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS040817] Funding Source: NIH RePORTER
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In addition to powering energy needs of the cell, mitochondria function as pivotal integrators of cell survival/death signals. In recent years, numerous studies indicate that each of the major kinase signaling pathways can be stimulated to target the mitochondrion. These include protein kinase A, protein kinase B/Akt, protein kinase C, extracellular signal-regulated protein kinase, c-Jun N-terminat kinase, and p38 mitogen-activated protein kinase. Although most studies focus on phosphorylation of pro- and antiapoptotic proteins (BAD, Bax, Bcl-2, Bcl-xL), kinase-mediated regulation of complex I activity, anion and cation channels, metabolic enzymes, and Mn-SOD mRNA has also been reported. Recent identification of a number of scaffold proteins (AKAP, PICK, Sab) that bring specific kinases to the cytoplasmic surface of mitochondria further emphasizes the importance of mitochondrial kinase signaling. Immunogold electron microscopy, subcellular fractionation, and immuno-fluorescence studies demonstrate the presence of kinases within subcompartments of the mitochondrion, following diverse stimuli and in neurodegenerative diseases. Given the sensitivity of these signaling pathways to reactive oxygen and nitrogen species, in situ activation of mitochondrial kinases may represent a potent reverse-signaling mechanism for communication of mitochondrial status to the rest of the cell. (C) 2004 Elsevier Inc. All rights reserved.
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