title: Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake.
abstract: Mitochondrial Ca(2+) homeostasis is fundamental to regulation of mitochondrial membrane potential, ATP production, and cellular Ca(2+) homeostasis. It has been known for decades that isolated mitochondria can take up Ca(2+) from the extramitochondrial solution, but the molecular identity of the Ca(2+) channels involved in this action is largely unknown. Here, we show that a fraction of canonical transient receptor potential 3 (TRPC3) channels is localized to mitochondria, a significant fraction of mitochondrial Ca(2+) uptake that relies on extramitochondrial Ca(2+) concentration is TRPC3-dependent, and the up- and down-regulation of TRPC3 expression in the cell influences the mitochondrial membrane potential. Our findings suggest that TRPC3 channels contribute to mitochondrial Ca(2+) uptake. We anticipate our observations may provide insights into the mechanisms of mitochondrial Ca(2+) uptake and advance understanding of the physiological role of TRPC3.
authors.affiliation: Laboratory of Neural Signal Transduction, Institute of Neuroscience, Shanghai Institutes of Biological Sciences, State Key Laboratory of Neuroscience, Shanghai 200031, China.
authors.forename: Shengjie
authors.initials: S
authors.lastname: Feng
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
authors.forename: Yilin
authors.initials: Y
authors.lastname: Tai
authors.forename: Junbo
authors.initials: J
authors.lastname: Huang
authors.forename: Yujuan
authors.initials: Y
authors.lastname: Su
authors.forename: Joel
authors.initials: J
authors.lastname: Abramowitz
authors.forename: Michael X
authors.initials: MX
authors.lastname: Zhu
authors.forename: Lutz
authors.initials: L
authors.lastname: Birnbaumer
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D017136:Ion Transport; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D050052:TRPC Cation Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D002118:Calcium