Mitochondria and Ca(2+) signaling: old guests, new functions.
Mitochondria are ancient endosymbiotic guests that joined the cells in the evolution of complex life. While the unique ability of mitochondria to produce adenosine triphosphate (ATP) and their contribution to cellular nutrition metabolism received condign attention, our understanding of the organelle's contribution to Ca(2+) homeostasis was restricted to serve as passive Ca(2+) sinks that accumulate Ca(2+) along the organelle's negative membrane potential. This paradigm has changed radically. Nowadays, mitochondria are known to respond to environmental Ca(2+) and to contribute actively to the regulation of spatial and temporal patterns of intracellular Ca(2+) signaling. Accordingly, mitochondria contribute to many signal transduction pathways and are actively involved in the maintenance of capacitative Ca(2+) entry, the accomplishment of Ca(2+) refilling of the endoplasmic reticulum and Ca(2+)-dependent protein folding. Mitochondrial Ca(2+) homeostasis is complex and regulated by numerous, so far, genetically unidentified Ca(2+) channels, pumps and exchangers that concertedly accomplish the organelle's Ca(2+) demand. Notably, mitochondrial Ca(2+) homeostasis and functions are crucially influenced by the organelle's structural organization and motility that, in turn, is controlled by matrix/cytosolic Ca(2+). This review intends to provide a condensed overview on the molecular mechanisms of mitochondrial Ca(2+) homeostasis (uptake, buffering and storage, extrusion), its modulation by other ions, kinases and small molecules, and its contribution to cellular processes as fundamental basis for the organelle's contribution to signaling pathways. Hence, emphasis is given to the structure-to-function and mobility-to-function relationship of the mitochondria and, thereby, bridging our most recent knowledge on mitochondria with the best-established mitochondrial function: metabolism and ATP production.
Graier
Wolfgang F
WF
Molecular and Cellular Physiology Research Unit, MCPRU, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria. wolfgang.graier@meduni-graz.at
Frieden
Maud
M
Malli
Roland
R
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D003600:Cytosol / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000502:physiology* / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000502:physiology; D024101:Mitochondrial Proteins / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism; D017510:Protein Folding; D017382:Reactive Oxygen Species / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D015220:Calcium Channels; D007473:Ion Channels; D024101:Mitochondrial Proteins; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C034703:mitochondrial calcium uniporter; D002118:Calcium