Mitochondrial [Ca2+] Oscillations Driven by Local High [Ca2+] Domains Generated by Spontaneous Electric Activity

• Published in: The Journal of biological chemistry Vol. 276; no. 43; pp. 40293 - 40297
• Main Authors: Villalobos, Carlos, Núñez, Lucı́a, Chamero, Pablo, Alonso, Marı́a Teresa, Garcı́a-Sancho, Javier
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 26.10.2001
• Subjects: Aequorin - biosynthesis; Aequorin - genetics; Animals; Calcium Signaling; Electrophysiology; Image Processing, Computer-Assisted; Life Sciences; Luminescent Measurements; Mitochondria - metabolism; Other; Oxygen Consumption; Pituitary Gland, Anterior - cytology; Pituitary Gland, Anterior - metabolism; Pituitary Hormones - metabolism; Rats
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C100465200

Mitochondria take up calcium during cell activation thus shaping Ca 2+ signaling and exocytosis. In turn, Ca 2+ uptake by mitochondria increases respiration and ATP synthesis. Targeted aequorins are excellent Ca 2+ probes for subcellular analysis, but single-cell imaging has proven difficult. Here we combine virus-based expression of targeted aequorins with photon-counting imaging to resolve dynamics of the cytosolic, mitochondrial, and nuclear Ca 2+ signals at the single-cell level in anterior pituitary cells. These cells exhibit spontaneous electric activity and cytosolic Ca 2+ oscillations that are responsible for basal secretion of pituitary hormones and are modulated by hypophysiotrophic factors. Aequorin reported spontaneous [Ca 2+ ] oscillations in all the three compartments, bulk cytosol, nucleus, and mitochondria. Interestingly, a fraction of mitochondria underwent much larger [Ca 2+ ] oscillations, which were driven by local high [Ca 2+ ] domains generated by the spontaneous electric activity. These oscillations were large enough to stimulate respiration, providing the basis for local tune-up of mitochondrial function by the Ca 2+ signal.