%0 Journal Article
%T Mitochondrial Markers for Cancer: Relevance to Diagnosis, Therapy, and Prognosis and General Understanding of Malignant Disease Mechanisms
%A Boel De Paepe
%J ISRN Pathology
%D 2012
%R 10.5402/2012/217162
%X Cancer cells display changes that aid them to escape from cell death, sustain their proliferative powers, and shift their metabolism toward glycolytic energy production. Mitochondria are key organelles in many metabolic and biosynthetic pathways, and the adaptation of mitochondrial function has been recognized as crucial to the changes that occur in cancer cells. This paper zooms in on the pathologic evaluation of mitochondrial markers for diagnosing and staging of human cancer and determining the patients¡¯ prognoses. 1. Introduction Mitochondria are membrane-enclosed cell organelles that can be found in all human cells, except for the peripheral red blood cells. An eukaryote cell contains around 1000 to 2000 mitochondria, with diameters varying between 0.5 and 1.0£¿¦Ìm. The mitochondrion is a key venue for cellular metabolism and the powerhouse of the cell. As a consequence, mitochondrial content is influenced by cellular energy demand. Exercise training for instance, increases the amount of mitochondria per fiber and the volume of organelles in skeletal muscle tissue [1, 2]. 1.1. Mitochondrial Metabolic Pathways To understand the crucial role played by mitochondria in cancer, it is necessary to fully grasp the extent of their metabolic activity. 1.1.1. Glycolysis Glycolysis is the sequence of cellular reactions that converts glucose into pyruvate, with the concomitant production of a relatively small amount of energy. Glycolysis occurs throughout the cell and is considered the basis of all energy processes. The 2 ATP and 2 NADH molecules it produces can enter the oxidative phosphorylation (OXPHOS) cycle, which then produces larger quantities of ATP. 1.1.2. Oxidative Phosphorylation In the Krebs or OXPHOS cycle, sequential oxidation and reduction reactions take place upon a chain of four multiprotein complexes: (1) complex I is composed of 45 protein subunits and displays NADH dehydrogenase activity. In the process, four hydrogen ions are pumped out of the mitochondrial matrix. (2) Complex II: the succinate dehydrogenase complex catalyzes the oxidation of succinate to fumarate, with concomitant reduction of ubiquinone. (3) In two cycles, complex III or coenzyme Q cytochrome c oxidoreductase reduces coenzyme Q, extracting 4 protons from the mitochondrial matrix. (4) On complex IV or cytochrome c oxidase, electrons are donated one at a time to cytochrome c and passed on to O2, producing 2 H2O molecules. In addition to the protons utilized in the reduction of O2, there is electron transfer-linked transport of 2 protons from the matrix to the mitochondrial
%U http://www.hindawi.com/journals/isrn.pathology/2012/217162/