PMID- 9151670
OWN - NLM
STAT- MEDLINE
DCOM- 19970602
LR  - 20240213
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 137
IP  - 3
DP  - 1997 May 5
TI  - Mitochondrial regulation of store-operated calcium signaling in T lymphocytes.
PG  - 633-48
AB  - Mitochondria act as potent buffers of intracellular Ca2+ in many cells, but a 
      more active role in modulating the generation of Ca2+ signals is not well 
      established. We have investigated the ability of mitochondria to modulate 
      store-operated or "capacitative" Ca2+ entry in Jurkat leukemic T cells and human 
      T lymphocytes using fluorescence imaging techniques. Depletion of the ER Ca2+ 
      store with thapsigargin (TG) activates Ca2+ release-activated Ca2+ (CRAC) 
      channels in T cells, and the ensuing influx of Ca2+ loads a TG-insensitive 
      intracellular store that by several criteria appears to be mitochondria. Loading 
      of this store is prevented by carbonyl cyanide m-chlorophenylhydrazone or by 
      antimycin A1 + oligomycin, agents that are known to inhibit mitochondrial Ca2+ 
      import by dissipating the mitochondrial membrane potential. Conversely, 
      intracellular Na+ depletion, which inhibits Na+-dependent Ca2+ export from 
      mitochondria, enhances store loading. In addition, we find that rhod-2 labels 
      mitochondria in T cells, and it reports changes in Ca2+ levels that are 
      consistent with its localization in the TG-insensitive store. Ca2+ uptake by the 
      mitochondrial store is sensitive (threshold is <400 nM cytosolic Ca2+), rapid 
      (detectable within 8 s), and does not readily saturate. The rate of mitochondrial 
      Ca2+ uptake is sensitive to extracellular [Ca2+], indicating that mitochondria 
      sense Ca2+ gradients near CRAC channels. Remarkably, mitochondrial uncouplers or 
      Na+ depletion prevent the ability of T cells to maintain a high rate of 
      capacitative Ca2+ entry over prolonged periods of >10 min. Under these 
      conditions, the rate of Ca2+ influx in single cells undergoes abrupt transitions 
      from a high influx to a low influx state. These results demonstrate that 
      mitochondria not only buffer the Ca2+ that enters T cells via store-operated Ca2+ 
      channels, but also play an active role in modulating the rate of capacitative 
      Ca2+ entry.
FAU - Hoth, M
AU  - Hoth M
AD  - Department of Molecular and Cellular Physiology, Stanford University School of 
      Medicine, California 94305-5426, USA. mhoth@leland.stanford.edu
FAU - Fanger, C M
AU  - Fanger CM
FAU - Lewis, R S
AU  - Lewis RS
LA  - eng
GR  - R01 GM045374/GM/NIGMS NIH HHS/United States
GR  - R37 GM045374/GM/NIGMS NIH HHS/United States
GR  - GM45374/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Calcium Channels)
RN  - 56092-81-0 (Ionomycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 9NEZ333N27 (Sodium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/*physiology
MH  - Calcium Channels/physiology
MH  - Cell Compartmentation
MH  - Cell Line
MH  - Endoplasmic Reticulum/metabolism
MH  - Humans
MH  - Ionomycin/pharmacology
MH  - Mitochondria/drug effects/*physiology
MH  - Signal Transduction
MH  - Sodium/metabolism
MH  - T-Lymphocytes/*physiology
MH  - Thapsigargin/pharmacology
MH  - Video Recording
PMC - PMC2139882
EDAT- 1997/05/05 00:00
MHDA- 1997/05/05 00:01
PMCR- 1997/11/05
CRDT- 1997/05/05 00:00
PHST- 1997/05/05 00:00 [pubmed]
PHST- 1997/05/05 00:01 [medline]
PHST- 1997/05/05 00:00 [entrez]
PHST- 1997/11/05 00:00 [pmc-release]
AID - 10.1083/jcb.137.3.633 [doi]
PST - ppublish
SO  - J Cell Biol. 1997 May 5;137(3):633-48. doi: 10.1083/jcb.137.3.633.