Long-term modulation of mitochondrial Ca2+ signals by protein kinase C isozymes.
The modulation of Ca2+ signaling patterns during repetitive stimulations represents an important mechanism for integrating through time the inputs received by a cell. By either overexpressing the isoforms of protein kinase C (PKC) or inhibiting them with specific blockers, we investigated the role of this family of proteins in regulating the dynamic interplay of the intracellular Ca2+ pools. The effects of the different isoforms spanned from the reduction of ER Ca2+ release (PKCalpha) to the increase or reduction of mitochondrial Ca2+ uptake (PKCzeta and PKCbeta/PKCdelta, respectively). This PKC-dependent regulatory mechanism underlies the process of mitochondrial Ca2+ desensitization, which in turn modulates cellular responses (e.g., insulin secretion). These results demonstrate that organelle Ca2+ homeostasis (and in particular mitochondrial processing of Ca2+ signals) is tuned through the wide molecular repertoire of intracellular Ca2+ transducers.
Pinton
Paolo
P
Section of General Pathology, Department of Experimental and Diagnostic Medicine, Via Borsari 46, 44100 Ferrara, Italy.
Leo
Sara
S
Wieckowski
Mariusz R
MR
Di Benedetto
Giulietta
G
Rizzuto
Rosario
R
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006632:Histamine / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011753:Pyrones / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D007527:Isoenzymes; D011753:Pyrones; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D006632:Histamine; D011493:Protein Kinase C; C007946:hispidin; D002118:Calcium