Mitochondrial kinases in cell signaling: Facts and perspectives.
Phylogenetic studies had shown that evolution of mitochondria occurred in parallel with the maturation of kinases implicated in growth and final size of modern organisms. In the last years, different reports confirmed that MAPKs, Akt, PKA and PKC are present in mitochondria, particularly in the intermembrane space and inner membrane where they meet mitochondrial constitutive upstream activators. Although a priori phosphorylation is the apparent aim of translocation, new perspectives indicate that kinase activation depends on redox status as determined by the mitochondrial production of oxygen species. We observed that the degree of mitochondrial oxidation of ERK Cys(38) and Cys(214) discriminates the kinase to be phosphorylated and determines translocation to the nuclear compartment and proliferation, or accumulation in mitochondria and arrest. Otherwise, transcriptional gene regulation by Akt depends on Cys(60) and Cys(310) oxidation to sulfenic and sulfonic acids. It is concluded that the interactions between kinases and mitochondria control cell signaling pathways and participate in the modulation of cell proliferation and arrest, tissue protection, tumorigenesis and cancer progression.
Antico Arciuch
Valeria G
VG
University Hospital, University of Buenos Aires, Argentina. vantico@hospitaldeclinicas.uba.ar
Alippe
Yael
Y
Carreras
María Cecilia
MC
Poderoso
Juan José
JJ
D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008928:Mitochondria / Q000201:enzymology* / Q000502:physiology*; D008954:Models, Biological; D009203:Myocardial Infarction / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D010084:Oxidation-Reduction; D011494:Protein Kinases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
D017382:Reactive Oxygen Species; D011494:Protein Kinases