A MITOCHONDRIAL MEMORY OF CA2+ SIGNALS: SENSING AND IMAGING SUBMITOCHONDRIAL CA2+ COMPARTMENTATION

Paolo Bernardi (1), Francesca De Giorgi (1), Carmen A. Mannella (2), Michael Marko (2), Raffaele Colonna (1) and Francois Ichas (1)
(1) CNR Center for the Study of Biomembranes and Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, I-35121 Padova, Italy
(2) Wadsworth Center, Division of Molecular Medicine, New York State Department of Health, Empire State Plaza, PO Box 509, Albany, NY 12201-0509, USA

Mitochondria actively contribute to intracellular Ca2+ signaling processes by taking up, and subsequently releasing into the cytosol large amounts of Ca2+. We report here that the chronology of mitochondrial Ca2+ uptake is recorded by mitochondria and retrieved during Ca2+ release. Indeed, Ca2+ is released from the organelle in a temporally-ordered manner that mirrors the chronology of Ca2+ uptake, cations accumulated first being released last. Such memory persists for minutes, indicating that mitochondrial Ca2+ is sorted and stored on a temporal basis, within an organized submitochondrial compartment. We find that the latter is accessible to the hydrophobic Ca2+ probe chlortetracycline, and that most of the Ca2+ taken up/released by mitochondria, is directly channeled to/from this submitochondrial compartment capable of chronological Ca2+ storage. Using ultrastructural imaging and spectroscopy (XMA), we find (as have others) that Ca2+ is stored at high concentration in specialized matrix regions (granules). When Ca2+ and Sr2+ are taken up sequentially, the Ca:Sr signal in different particles is approximately constant, suggesting possible compartmentation within the granules. There is also detectable Sr signal in some intracristal spaces, which may represent another functional compartment. These results indicate that mitochondria can memorize the chronology of Ca2+ signals, and that such memory may be dependent on the spatial organization of Ca2+ within the organelle.