University of California, San Francisco (UCSF)

Molecular Mechanisms Governing Mitochondrial Calcium Uptake

Research Area

Grant Type



Mitochondrial dysfunction and derangement of intracellular Ca2+ homeostasis are two major factors leading to cell damage in aging and neurodegenerative diseases; however, the origins of these two factors themselves remain poorly understood. Interestingly, mitochondria accumulate significant amounts of Ca2+ during cytosolic Ca2+ elevations. Experimental evidence suggests that derangement in the mitochondrial Ca2+ handling may cause both, derangement in intracellular Ca2+ homeostasis and mitochondrial dysfunction. Mitochondria accumulate cytosolic Ca2+ via an elusive transport mechanism of the inner mitochondrial membrane called the mitochondrial Ca2+ uniporter (MCU).

Recently, we developed a method for direct recording Ca2+ currents flowing across the native inner mitochondrial membrane, and showed that the MCU is a novel, highly selective Ca2+ channel. We are using this technique in combination with the molecular genetics to identify the proteins in the inner mitochondrial membrane that form the pore of the MCU channel and to characterize molecular mechanisms that regulate its activity. This research will help to elucidate the physiological roles of the MCU and mitochondrial Ca2+ uptake and to understand their involvement in aging and neurodegenerative diseases. The work may also suggest pharmacologic approaches to modulate activity of the MCU and slow down the progression of age-related pathological conditions.