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Mitochondrial Ca(2+)-induced Ca(2+) release mediated by the Ca(2+) uniporter
M Montero1, M T Alonso, A Albillos
1Instituto de Biología y Genética Molecular, Universidad de Valladolid y Consejo Superior de Investigaciones Científicas, Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, E-47005 Valladolid, Spain.
Molecular Biology of the Cell
|February 13, 2001
Summary
Chromaffin cell mitochondria absorb significant calcium (Ca2+) during stimulation. This study reveals a novel mitochondrial Ca2+ release pathway, potentially aiding Ca2+ clearance during overload.
Area of Science:
- Cellular biology
- Mitochondrial function
- Calcium signaling
Background:
- Chromaffin cell mitochondria accumulate substantial Ca2+ upon stimulation.
- Understanding mitochondrial Ca2+ efflux pathways is crucial for cellular homeostasis.
Purpose of the Study:
- To investigate the mechanisms of mitochondrial Ca2+ efflux from chromaffin cells.
- To identify the specific pathways involved in releasing Ca2+ from mitochondria.
Main Methods:
- Utilized protonophores and specific inhibitors (CGP37157, ruthenium red, valinomycin, nigericin) to study mitochondrial Ca2+ handling.
- Measured cytosolic Ca2+ ([Ca2+](c)) dynamics and mitochondrial Ca2+ content in intact and permeabilized cells.
- Examined the role of mitochondrial Na+/Ca2+ exchange and the Ca2+ uniporter in Ca2+ efflux.
Main Results:
- Protonophores, when added post-stimulation, inhibited Ca2+ release from loaded mitochondria by blocking Na+/Ca2+ exchange.
- Elevated extramitochondrial Ca2+ induced rapid Ca2+ release from depolarized mitochondria.
- This Ca2+-induced Ca2+ release was insensitive to cyclosporin A and CGP37157 but blocked by ruthenium red, suggesting Ca2+ uniporter reversal.
Conclusions:
- A novel mitochondrial Ca2+-induced Ca2+ release mechanism, potentially via Ca2+ uniporter reversal, has been identified.
- This pathway may play a significant role in clearing excess Ca2+ from depolarized mitochondria during Ca2+ overload.