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Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion
M Montero1, M T Alonso, E Carnicero
1Instituto de Biología y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, Ramón y Cajal 7, E-4700, Spain.
Nature Cell Biology
|February 3, 2000
Summary
Mitochondria rapidly take up calcium ions (Ca2+) during cell stimulation, reaching millimolar levels. This mitochondrial Ca2+ uptake influences catecholamine secretion, suggesting mitochondria regulate exocytosis.
Area of Science:
- Cellular Biology
- Neuroscience
- Mitochondrial Function
Background:
- Calcium ions (Ca2+) are critical signaling molecules involved in various cellular processes.
- Mitochondria play a role in cellular calcium homeostasis and energy metabolism.
- The precise role of mitochondria in regulating exocytosis, particularly in chromaffin cells, remains an area of active investigation.
Purpose of the Study:
- To investigate the rapid calcium transients within mitochondria during cell stimulation.
- To elucidate the functional coupling between plasma membrane Ca2+ channels, endoplasmic reticulum Ca2+ stores, and mitochondria.
- To determine the impact of mitochondrial Ca2+ uptake on catecholamine secretion from chromaffin cells.
Main Methods:
- Utilized mitochondrially targeted aequorin proteins with varying Ca2+ affinities to measure mitochondrial Ca2+ concentrations.
- Stimulated chromaffin cells using acetylcholine, caffeine, and high potassium concentrations.
- Employed protonophores to assess the role of mitochondrial Ca2+ uptake in secretion.
Main Results:
- Observed rapid, high-amplitude (millimolar) Ca2+ transients in approximately half of chromaffin cell mitochondria upon stimulation.
- Demonstrated tight functional coupling between plasma membrane Ca2+ channels, ryanodine receptors, and mitochondria.
- Showed that protonophores inhibiting mitochondrial Ca2+ uptake increased stimulated catecholamine secretion by 3-5 fold.
Conclusions:
- Mitochondria exhibit rapid and significant Ca2+ uptake during physiological stimulation of chromaffin cells.
- Mitochondria are tightly integrated with Ca2+ release channels, forming functional units that generate localized high Ca2+ transients.
- Mitochondrial Ca2+ uptake plays a crucial role in modulating catecholamine exocytosis, indicating mitochondria actively regulate secretion.