TY - JOUR AU - Szabadkai, G AU - Bianchi, K AU - Várnai, Péter AU - De Stefani, D AU - Wieckowski, MR AU - Cavagna, D AU - Nagy, Anikó Ilona AU - Balla, Tamás AU - Rizzuto, R TI - Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channels. JF - JOURNAL OF CELL BIOLOGY J2 - J CELL BIOL VL - 175 PY - 2006 IS - 6 SP - 901 EP - 911 PG - 11 SN - 0021-9525 DO - 10.1083/jcb.200608073 UR - https://m2.mtmt.hu/api/publication/1133064 ID - 1133064 AB - The voltage-dependent anion channel (VDAC) of the outer mitochondrial membrane mediates metabolic flow, Ca(2+), and cell death signaling between the endoplasmic reticulum (ER) and mitochondrial networks. We demonstrate that VDAC1 is physically linked to the endoplasmic reticulum Ca(2+)-release channel inositol 1,4,5-trisphosphate receptor (IP(3)R) through the molecular chaperone glucose-regulated protein 75 (grp75). Functional interaction between the channels was shown by the recombinant expression of the ligand-binding domain of the IP(3)R on the ER or mitochondrial surface, which directly enhanced Ca(2+) accumulation in mitochondria. Knockdown of grp75 abolished the stimulatory effect, highlighting chaperone-mediated conformational coupling between the IP(3)R and the mitochondrial Ca(2+) uptake machinery. Because organelle Ca(2+) homeostasis influences fundamentally cellular functions and death signaling, the central location of grp75 may represent an important control point of cell fate and pathogenesis. LA - English DB - MTMT ER - TY - JOUR AU - Starkov, AA AU - Chinopoulos, Christos AU - Fiskum, G TI - Mitochondrial calcium and oxidative stress as mediators of ischemic brain injury JF - CELL CALCIUM J2 - CELL CALCIUM VL - 36 PY - 2004 IS - 3-4 SP - 257 EP - 264 PG - 8 SN - 0143-4160 DO - 10.1016/j.ceca.2004.02.012 UR - https://m2.mtmt.hu/api/publication/1486705 ID - 1486705 LA - English DB - MTMT ER - TY - JOUR AU - Tretter, László AU - Ádám, Veronika TI - Generation of reactive oxygen species in the reaction catalyzed by alpha-ketoglutarate dehydrogenase JF - JOURNAL OF NEUROSCIENCE J2 - J NEUROSCI VL - 24 PY - 2004 IS - 36 SP - 7771 EP - 7778 PG - 8 SN - 0270-6474 DO - 10.1523/JNEUROSCI.1842-04.2004 UR - https://m2.mtmt.hu/api/publication/1030897 ID - 1030897 LA - English DB - MTMT ER - TY - JOUR AU - Csordas, G AU - Thomas, AP AU - Hajnóczky, György TI - Quasi-synaptic calcium signal transmission between endoplasmic reticulum and mitochondria JF - EMBO JOURNAL J2 - EMBO J VL - 18 PY - 1999 IS - 1 SP - 96 EP - 108 PG - 13 SN - 0261-4189 DO - 10.1093/emboj/18.1.96 UR - https://m2.mtmt.hu/api/publication/1688418 ID - 1688418 AB - Transmission of cytosolic [Ca2+] ([Ca2+](c)) oscillations into the mitochondrial matrix is thought to be supported by local calcium control between IP3 receptor Ca2+ channels (IP3R) and mitochondria, but study of the coupling mechanisms has been difficult. We established a permeabilized cell model in which the Ca2+ coupling between endoplasmic reticulum (ER) and mitochondria is retained, and mitochondrial [Ca2+] ([Ca2+](m)) can be monitored by fluorescence imaging. We demonstrate that maximal activation of mitochondrial Ca2+ uptake is evoked by IP3-induced perimitochondrial [Ca2+] elevations, which appear to reach values >20-fold higher than the global increases of [Ca2+](c), Incremental doses of IP3 elicited [Ca2+](m) elevations that followed the quantal pattern of Ca2+ mobilization, even at the level of individual mitochondria, In contrast, gradual increases of IP3 evoked relatively small [Ca2+](m) responses despite eliciting similar [Ca2+](c) increases. We conclude that each mitochondrial Ca2+ uptake site faces multiple IP3R, a concurrent activation of which is required for optimal activation of mitochondrial Ca2+ uptake. This architecture explains why calcium oscillations evoked by synchronized periodic activation of IP3R are particularly effective in establishing dynamic control over mitochondrial metabolism. Furthermore, our data reveal fundamental functional similarities between ER-mitochondrial Ca2+ coupling and synaptic transmission. LA - English DB - MTMT ER - TY - JOUR AU - Hajnóczky, György AU - ROBBGASPERS, LD AU - SEITZ, MB AU - THOMAS, AP TI - DECODING OF CYTOSOLIC CALCIUM OSCILLATIONS IN THE MITOCHONDRIA JF - CELL J2 - CELL VL - 82 PY - 1995 IS - 3 SP - 415 EP - 424 PG - 10 SN - 0092-8674 DO - 10.1016/0092-8674(95)90430-1 UR - https://m2.mtmt.hu/api/publication/1690267 ID - 1690267 AB - Frequency-modulated oscillations of cytosolic Ca2+ ([Ca2+](c)) are believed to be important in signal transduction, but it has been difficult to correlate [Ca2+](c) oscillations directly with the activity of Ca2+-regulated targets. We have studied the control of Ca2+-sensitive mitochondrial dehydrogenases (CSMDHs) by monitoring mitochondrial Ca2+ ([Ca2+](m)) and the redox state of flavoproteins and pyridine nucleotides simultaneously with [Ca2+](c) in single hepatocytes. Oscillations of [Ca2+](c) induced by IP3-dependent hormones were efficiently transmitted to the mitochondria as [Ca2+](m) oscillations. Each [Ca2+](m) spike was sufficient to cause a maximal transient activation of the CSMDHs and [Ca2+](m) oscillations at frequencies above 0.5 per minute caused a sustained activation of mitochondrial metabolism. By contrast, sustained [Ca2+](c) increases yielded only transient CSMDH activation, and slow or partial [Ca2+](c) elevations were ineffective in increasing [Ca2+](m) or stimulating CSMDHs. We conclude that the mitochondria are tuned to oscillating [Ca2+](c) signals, the frequency of which can control the CSMDHs over the full range of potential activities. LA - English DB - MTMT ER - TY - JOUR AU - Lukács, Gergely AU - Kapus, A TI - MEASUREMENT OF THE MATRIX FREE CA-2+ CONCENTRATION IN HEART- MITOCHONDRIA BY ENTRAPPED FURA-2 AND QUIN2 JF - BIOCHEMICAL JOURNAL J2 - BIOCHEM J VL - 248 PY - 1987 SP - 609 EP - 613 PG - 5 SN - 0264-6021 DO - 10.1042/bj2480609 UR - https://m2.mtmt.hu/api/publication/11010306 ID - 11010306 LA - English DB - MTMT ER -