The contribution of UCP2 and UCP3 to mitochondrial Ca(2+) uptake is differentially determined by the source of supplied Ca(2+).
The transmission of Ca(2+) signals to mitochondria is an important phenomenon in cell signaling. We have recently reported that the novel uncoupling proteins UCP2 and UCP3 (UCP2/3) are fundamental for mitochondrial Ca(2+) uniport (MCU). In the present study we investigate the contribution of UCP2/3 to mitochondrial accumulation of Ca(2+) either exclusively released from the ER or entering the cell via the store-operated Ca(2+) entry (SOCE) pathway. Using siRNA we demonstrate that constitutively expressed UCP2/3 are essentially involved in mitochondrial sequestration of intracellularly released Ca(2+) but not of that entering the cells via SOCE. However, overexpression of UCP2/3 yielded elevated mitochondrial Ca(2+) uptake from both sources, though it was more pronounced in case of entering Ca(2+), indicating that the expression levels of UCP2/3 are crucial for the capacity of mitochondria to sequester entering Ca(2+). Our data point to distinct UCP2/3-dependent and UCP2/3-independent modes of mitochondrial Ca(2+) sequestration, which may meet the various demands necessary for an adequate organelle Ca(2+) loading from different Ca(2+) sources in intact cells.
Waldeck-Weiermair
Markus
M
Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Austria.
Malli
Roland
R
Naghdi
Shamim
S
Trenker
Michael
M
Kahn
Muhammad Jadoon
MJ
Graier
Wolfgang F
WF
D002118:Calcium / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D007473:Ion Channels; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D002118:Calcium