title: The interplay of mitochondria with calcium: an historical appraisal.
abstract: Indirect findings in the 1950s had indicated that mitochondria could accumulate Ca(2+), but only in 1961 isolated mitochondria were directly shown to take it up in a process driven by the activity of the respiratory chain or by the hydrolysis of added ATP. The uptake of Ca(2+) could be accompanied by the simultaneous uptake of inorganic phosphate, leading to the precipitation of hydroxyapatite in the matrix and to the effective buffering of the free Ca(2+) concentration in it. The uptake of Ca(2+) occurred via an electrophoretic uniporter that has been molecularly identified only recently. Ca(2+) was then released through a Na(+)/Ca(2+) exchanger that has also been identified very recently (a H(+)/Ca(2+) antiporter has also been described in some mitochondrial types). In the matrix two TCA cycle dehydrogenases and pyruvate dehydrogenase phosphate phosphatase were found to be regulated by Ca(2+), providing a rationale for the Ca(2+) cycling process. The affinity of the uptake uniporter was found to be too low to efficiently regulate Ca(2+) in the low to mid nM concentration in the cytosol. However, a number of findings showed that energy linked transport of Ca(2+) did nevertheless occur in mitochondria in situ. The enigma was solved in the 1990s, when it was found that perimitochondrial Ca(2+) pools are created by the discharge of Ca(2+) from vicinal endoplasmic reticulum stores in which the concentration of Ca(2+) is high enough to satisfy the poor affinity of the uniporter. Thus, mitochondria have now regained a key role in the regulation of cytosolic Ca(2+) (not only of their own internal Ca(2+)).
authors.affiliation: Venetian Institute of Molecular Medicine, University of Padova, Italy. ernesto.carafoli@unipd.it
authors.forename: Ernesto
authors.initials: E
authors.lastname: Carafoli
mesh_terms: D000818:Animals; D002118:Calcium / Q000266:history / Q000378:metabolism*; D015220:Calcium Channels / Q000266:history / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D049673:History, 20th Century; D007477:Ions / Q000737:chemistry; D008928:Mitochondria / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000266:history / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D007477:Ions; D010710:Phosphates; D019831:Sodium-Calcium Exchanger; C034703:mitochondrial calcium uniporter; D010088:Oxidoreductases; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; D002118:Calcium