Ph.D Thesis

Ph.D StudentTali Kizhner
SubjectMolecular and Biochemical Modifications Induced by Reducing
Sugars in the Mitochondria
DepartmentDepartment of Biotechnology and Food Engineering
Supervisors Full Professors Machluf Marcelle
Mr. Werman Moshe


Current interest in fructose metabolism and chemical properties has arisen because of its increased use in the food industry in the crystalline form and as high-fructose corn syrup. During the last decades, the importance of mitochondria as a major contributor to various types of diseases and to aging has become apparent. This research was undertaken to find and characterize the possible metabolic events, induced by fructose as compared to glucose in the mitochondria. We performed an extensive analysis of different parameters at three molecular levels: mtDNA, RNA and protein. Cytotoxicity experiments in muscle cell culture suggested that carbohydrate effects were dose- and time-dependent. The estimation of the mtDNA susceptibility to reducing sugars demonstrates that fructose consumption causes minor modifications to the mtDNA.  Following 17 months drinking of fructose solutions we observed a significant decrease in the activity of the main mitochondrial antioxidant - manganese superoxide dismutase. Various genes expression patterns reflected the attempts of nuclear regulation machinery to balance the non-desirable changes in mitochondrial functioning in a tissue dependent manner. The results indicated that the liver is the main target of fructose influence, although there are minor alterations in postmitotic tissue (skeletal muscles and brain). Electron microscopy analysis of skeletal muscles obtained from mice maintained on fructose solutions, revealed some pathological alterations in their mitochondrial morphology. Taking all together, these findings implicate that fructose has a negative impact on the biological machinery of the mammalian mitochondria, pointing out the need for reconsideration fructose extensive use in food industry.