Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses.
The spatial relation between mitochondria and endoplasmic reticulum (ER) in living HeLa cells was analyzed at high resolution in three dimensions with two differently colored, specifically targeted green fluorescent proteins. Numerous close contacts were observed between these organelles, and mitochondria in situ formed a largely interconnected, dynamic network. A Ca2+-sensitive photoprotein targeted to the outer face of the inner mitochondrial membrane showed that, upon opening of the inositol 1,4,5-triphosphate (IP3)-gated channels of the ER, the mitochondrial surface was exposed to a higher concentration of Ca2+ than was the bulk cytosol. These results emphasize the importance of cell architecture and the distribution of organelles in regulation of Ca2+ signaling.
Rizzuto
R
R
Department of Biomedical Sciences and the National Research Council Center for the Study of Biomembranes, University of Padova, Via Colombo 3, 35121 Padova, Italy. rizzuto@civ.bio.unipd.it
Pinton
P
P
Carrington
W
W
Fay
F S
FS
Fogarty
K E
KE
Lifshitz
L M
LM
Tuft
R A
RA
Pozzan
T
T
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000331:Aequorin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002451:Cell Compartmentation; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D015640:Ion Channel Gating; D008164:Luminescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
D015220:Calcium Channels; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D000331:Aequorin; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D000255:Adenosine Triphosphate; D002118:Calcium