title: Mitochondria and chromaffin cell function.
abstract: Chromaffin cells are an excellent model for stimulus-secretion coupling. Ca(2+) entry through plasma membrane voltage-operated Ca(2+) channels (VOCC) is the trigger for secretion, but the intracellular organelles contribute subtle nuances to the Ca(2+) signal. The endoplasmic reticulum amplifies the cytosolic Ca(2+) ([Ca(2+)](C)) signal by Ca(2+)-induced Ca(2+) release (CICR) and helps generation of microdomains with high [Ca(2+)](C) (HCMD) at the subplasmalemmal region. These HCMD induce exocytosis of the docked secretory vesicles. Mitochondria close to VOCC take up large amounts of Ca(2+) from HCMD and stop progression of the Ca(2+) wave towards the cell core. On the other hand, the increase of [Ca(2+)] at the mitochondrial matrix stimulates respiration and tunes energy production to the increased needs of the exocytic activity. At the end of stimulation, [Ca(2+)](C) decreases rapidly and mitochondria release the Ca(2+) accumulated in the matrix through the Na(+)/Ca(2+) exchanger. VOCC, CICR sites and nearby mitochondria form functional triads that co-localize at the subplasmalemmal area, where secretory vesicles wait ready for exocytosis. These triads optimize stimulus-secretion coupling while avoiding propagation of the Ca(2+) signal to the cell core. Perturbation of their functioning in neurons may contribute to the genesis of excitotoxicity, ageing mental retardation and/or neurodegenerative disorders.
authors.affiliation: Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid and CSIC, c/Sanz y Forés, 3, 47003, Valladolid, Spain. jgsancho@ibgm.uva.es
authors.forename: Javier
authors.initials: J
authors.lastname: García-Sancho
authors.forename: Antonio M G
authors.initials: AM
authors.lastname: de Diego
authors.forename: Antonio G
authors.initials: AG
authors.lastname: García
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005089:Exocytosis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D022142:Secretory Vesicles / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D002118:Calcium