Essential role of aralar in the transduction of small Ca2+ signals to neuronal mitochondria
Aralar, the neuronal Ca2+-binding mitochondrial aspartate-glutamate carrier, has Ca2+ binding domains facing the extramitochondrial space and functions in the malate-aspartate NADH shuttle (MAS). Here we showed that MAS activity in brain mitochondria is stimulated by extramitochondrial Ca2+ with an...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2006 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/709527 |
| Acceso en línea: | http://hdl.handle.net/10486/709527 https://dx.doi.org/10.1074/jbc.M507270200 |
| Access Level: | acceso abierto |
| Palabra clave: | Mitochondrial Calcium Uniporter Animals Liver Mitochondrion Biología y Biomedicina / Biología |
| Sumario: | Aralar, the neuronal Ca2+-binding mitochondrial aspartate-glutamate carrier, has Ca2+ binding domains facing the extramitochondrial space and functions in the malate-aspartate NADH shuttle (MAS). Here we showed that MAS activity in brain mitochondria is stimulated by extramitochondrial Ca2+ with an S0.5 of 324 nM. By employing primary neuronal cultures from control and aralar-deficient mice and NAD(P)H imaging with two-photon excitation microscopy, we showed that lactate utilization involves a substantial transfer of NAD(P)H to mitochondria in control but not aralar-deficient neurons, in agreement with the lack of MAS activity associated with aralar deficiency. The increase in mitochondrial NAD(P)H was greatly potentiated by large [Ca2+]i signals both in control and aralar-deficient neurons, showing that these large signals activate the Ca2+ uniporter and mitochondrial dehydrogenases but not MAS activity. On the other hand, small [Ca2+]i signals potentiate the increase in mitochondrial NAD(P)H only in control but not in aralar-deficient neurons. We concluded that neuronal MAS activity is selectively activated by small Ca2+ signals that fall below the activation range of the Ca2+ uniporter and plays an essential role in mitochondrial Ca2+ signaling |
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