Redox proteins in mammalian cell death: an evolutionarily conserved function in mitochondria and prokaryotes.
Mammalian cell mitochondria are believed to have prokaryotic ancestry. Mitochondria are not only the powerhouse of energy generation within the eukaryotic cell but they also play a major role in inducing apoptotic cell death through release of redox proteins such as cytochrome c and the apoptosis-inducing factor (AIF), a flavoprotein with NADH oxidase activity. Recent evidence indicates that some present day prokaryotes release redox proteins that induce apoptosis in mammalian cells through stabilization of the tumour suppressor protein p53. p53 interacts with mitochondria either directly or through activation of the genes for pro-apoptotic proteins such as Bax or NOXA or genes that encode redox enzymes responsible for the production of reactive oxygen species (ROS). The analogy between the ancient ancestors of present day bacteria, the mitochondria, and the present day bacteria with regard to their ability to release redox proteins for triggering mammalian cell death is an interesting example of functional conservation during the hundreds of millions of years of evolution. It is possible that the ancestors of the present day prokaryotes released redox proteins to kill the ancestors of the eukaryotes. During evolution of the mitochondria from prokaryotes as obligate endosymbionts, the mitochondria maintained the same functions to programme their own host cell death.
Punj
Vasu
V
Department of Microbiology and Immunology, University of Illinois College of Medicine, 835 S. Wolcott Avenue, Chicago, IL 60612, USA.
Chakrabarty
A M
AM
D000595:Amino Acid Sequence; D001400:Azurin / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005075:Biological Evolution; D016923:Cell Death / Q000502:physiology*; D003574:Cytochrome c Group / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011387:Prokaryotic Cells / Q000378:metabolism*; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured
D001426:Bacterial Proteins; D003574:Cytochrome c Group; D001400:Azurin