Electrophysiological and molecular characterization of the mitochondrial Ca2+ uniporter (MCU) and mechanisms of its regulation.
The MCU is a highly selective Ca2+ channel of the inner mitochondrial membrane responsible for mitochondrial Ca2+ accumulation during intracellular Ca2+ signaling. It is important for regulating the rate of mitochondrial ATP production, shaping intracellular Ca2+ signals, and initiating both necrotic and apoptotic cell death. The MCU also has been implicated in regulation of ROS production by mitochondria and thus likely plays an important role in aging and neurodegenerative diseases. Unfortunately molecular identity of this important channel and its mechanisms of regulation remain unknown. We hope to solve this problem and learn more about physiological and pathophysiological roles of the MCU.
Comprehensive identification and electrophysiological characterization of mitochondrial ion channels using single-channel and whole-membrane patch clamp recordings from the native inner mitochondrial membrane.
In addition to the MCU, the inner mitochondrial membrane contains proton, potassium and chloride channels as well as a large non-selective pore called the permeability transition pore (PTP). These ion channels, mechanisms of their regulation and their physiological functions remain largely unexplored. We plan to establish the full complement of ion channels located in IMM and prepare basis for their molecular characterization. These results will help us better understand physiological and pathophysiological roles of electrical signaling in mitochondria.
Yuriy Kirichok earned his undergraduate degree from Moscow Institute of Physics and Technology before pursuing a PhD in Biophysics at Bogomoletz Institute of Physiology in Kiev, Ukraine. He completed subsequent postdoctoral research at Harvard Medical School before joining the Physiology Department at UCSF.
Dr. Kirichok holds the Jack D. and DeLoris Lange Endowed Chair in Systems Physiology II.
Jose Carlos de Lima Jr., MD., PhD, Postdoctoral Fellow
Junji Suzuki, Postdoctoral fellow
Francesca Fieni, Specialist