Lecturer : Dr. Ali Ferjani (Associate Professor, Department of Biology,Tokyo Gakugei University)
フェルジャ二アリ先生(東京学芸大学自然科学系生命科学分野 准教授)
Title : The metabolic catastrophe of PPi over-accumulation:Major targets and potential benefits
Date : Monday, January 19, 2015
Time : 16:00 - 17:30
Place : 2F Seminar room, BioSystems Building, Graduate School of Frontier Biosciences
Host : Tamotsu Yoshimori (Laboratory of Intracellular Membrane Dynamics)
Phone : 06-6879-3585
Abstract :
Pyrophosphate (PPi) is generated in anabolic reactions such as synthesis of UDP-glucose, the substrate for glycogen synthesis in animals and cellulose in plants. Until recently, the biological roles of PPi were obscured because loss of pyrophosphatase (PPase) activity caused growth arrest, and developmental defects in many organisms, hampering in depth investigation. Our screening identified fugu5 as a viable H+-PPase loss-of-function mutant of Arabidopsis thaliana. In the first half of this seminar, I will present detailed functional analysis of H+-PPase, and show that elevated level of cytosolic PPi inhibits gluconeogenesis. Then, I will present our metabolomics data which identified UDP-glucose pyrophosphorylase as the major target of PPi in vivo. Finally, being highly expressed in several cancer cell types, PPase may represent a unique target for cancer therapy.
フェルジャ二アリ先生(東京学芸大学自然科学系生命科学分野 准教授)
Title : The metabolic catastrophe of PPi over-accumulation:Major targets and potential benefits
Date : Monday, January 19, 2015
Time : 16:00 - 17:30
Place : 2F Seminar room, BioSystems Building, Graduate School of Frontier Biosciences
Host : Tamotsu Yoshimori (Laboratory of Intracellular Membrane Dynamics)
Phone : 06-6879-3585
Abstract :
Pyrophosphate (PPi) is generated in anabolic reactions such as synthesis of UDP-glucose, the substrate for glycogen synthesis in animals and cellulose in plants. Until recently, the biological roles of PPi were obscured because loss of pyrophosphatase (PPase) activity caused growth arrest, and developmental defects in many organisms, hampering in depth investigation. Our screening identified fugu5 as a viable H+-PPase loss-of-function mutant of Arabidopsis thaliana. In the first half of this seminar, I will present detailed functional analysis of H+-PPase, and show that elevated level of cytosolic PPi inhibits gluconeogenesis. Then, I will present our metabolomics data which identified UDP-glucose pyrophosphorylase as the major target of PPi in vivo. Finally, being highly expressed in several cancer cell types, PPase may represent a unique target for cancer therapy.