On June 17th, 2013, a study from the Laboratory of Neural Signal Transduction at the Institute of Neuroscience, Chinese Academy of Sciences, was published online in PNAS as a research article entitled "Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake". This work was mainly carried out by graduate students Shengjie Feng, Hongyu Li and Yilin Tai, under the supervision of Dr. Yizheng Wang, in collaboration with Dr. Lutz Birnbaumer's laboratory from the NIH in the U.S.A.

　　Mitochondrial Ca²⁺ uptake is critical for regulation of numerous cellular processes, including energy metabolism and cytosolic Ca²⁺ homeostasis. Mitochondria undergo rapid changes in matrix Ca²⁺ concentration ([Ca²⁺]mito) upon cell stimulation to affect aerobic metabolism and cell survival. Mitochondrial Ca²⁺ homeostasis is fundamental to regulation of mitochondrial membrane potential, ATP production and cellular Ca²⁺ homeostasis. It has been known for decades that isolated mitochondria can take up Ca²⁺ from the extra-mitochondrial solution, but the molecular identity of the Ca²⁺ channels involved for this action is largely unknown. This study from the Wang lab found that a fraction of canonical transient receptor potential 3 (TRPC3) channels localized to mitochondria, a significant amount of mitochondrial Ca²⁺ uptake relying on extra-mitochondrial Ca²⁺ concentration is TRPC3-dependent, and up and down regulation of TRPC3 expression in the cell influences mitochondrial membrane potential.

　　These findings suggest that TRPC3 channels contribute to mitochondrial Ca²⁺ uptake and may provide new insights into the mechanisms of mitochondrial Ca²⁺ uptake and advance understanding of the physiological role of TRPC3.

　　This work was supported in part by grants from NNSF of China and the 973 program of MOST.

　　The results of western blot (A) and immunochemistry (B) showed mitochondrial localization of TRPC3 channels.