Difference between revisions of "Raturi 2016 J Cell Biol"
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|journal=J Cell Biol | |journal=J Cell Biol | ||
|abstract=The flux of Ca<sup>2+</sup> from the endoplasmic reticulum (ER) to mitochondria regulates mitochondria metabolism. Within tumor tissue, mitochondria metabolism is frequently repressed, leading to chemotherapy resistance and increased growth of the tumor mass. Therefore, altered ER-mitochondria Ca<sup>2+</sup> flux could be a cancer hallmark, but only a few regulatory proteins of this mechanism are currently known. One candidate is the redox-sensitive oxidoreductase TMX1 that is enriched on the mitochondria-associated membrane (MAM), the site of ER-mitochondria Ca<sup>2+</sup> flux. Our findings demonstrate that cancer cells with low TMX1 exhibit increased ER Ca<sup>2+</sup>, accelerated cytosolic Ca<sup>2+</sup> clearance, and reduced Ca<sup>2+</sup> transfer to mitochondria. Thus, low levels of TMX1 reduce ER-mitochondria contacts, shift bioenergetics away from mitochondria, and accelerate tumor growth. For its role in intracellular ER-mitochondria Ca<sup>2+</sup> flux, TMX1 requires its thioredoxin motif and palmitoylation to target to the MAM. As a thiol-based tumor suppressor, TMX1 increases mitochondrial ATP production and apoptosis progression. | |abstract=The flux of Ca<sup>2+</sup> from the endoplasmic reticulum (ER) to mitochondria regulates mitochondria metabolism. Within tumor tissue, mitochondria metabolism is frequently repressed, leading to chemotherapy resistance and increased growth of the tumor mass. Therefore, altered ER-mitochondria Ca<sup>2+</sup> flux could be a cancer hallmark, but only a few regulatory proteins of this mechanism are currently known. One candidate is the redox-sensitive oxidoreductase TMX1 that is enriched on the mitochondria-associated membrane (MAM), the site of ER-mitochondria Ca<sup>2+</sup> flux. Our findings demonstrate that cancer cells with low TMX1 exhibit increased ER Ca<sup>2+</sup>, accelerated cytosolic Ca<sup>2+</sup> clearance, and reduced Ca<sup>2+</sup> transfer to mitochondria. Thus, low levels of TMX1 reduce ER-mitochondria contacts, shift bioenergetics away from mitochondria, and accelerate tumor growth. For its role in intracellular ER-mitochondria Ca<sup>2+</sup> flux, TMX1 requires its thioredoxin motif and palmitoylation to target to the MAM. As a thiol-based tumor suppressor, TMX1 increases mitochondrial ATP production and apoptosis progression. | ||
|keywords=A375P human melanoma cells | |||
|editor=[[Kandolf G]] | |editor=[[Kandolf G]] | ||
|mipnetlab=CA Edmonton Zaugg M | |mipnetlab=CA Edmonton Zaugg M | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Genetic knockout;overexpression | ||
|organism=Human, Mouse | |organism=Human, Mouse | ||
|tissues=HeLa | |tissues=Other cell lines, HeLa | ||
|preparations=Intact cells, Permeabilized cells | |preparations=Intact cells, Permeabilized cells | ||
|topics=Calcium | |topics=Calcium | ||
|couplingstates=LEAK, ET | |couplingstates=LEAK, ROUTINE, ET | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional= | |additional=2017-07, | ||
}} | }} | ||
Latest revision as of 11:51, 26 June 2019
| Raturi A, Gutiérrez T, Ortiz-Sandoval C, Ruangkittisakul A, Herrera-Cruz MS, Rockley JP, Gesson K, Ourdev D, Lou PH, Lucchinetti E, Tahbaz N, Zaugg M, Baksh S, Ballanyi K, Simmen T (2016) TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux. J Cell Biol 214:433-44. |
Raturi A, Gutierrez T, Ortiz-Sandoval C, Ruangkittisakul A, Herrera-Cruz MS, Rockley JP, Gesson K, Ourdev D, Lou PH, Lucchinetti E, Tahbaz N, Zaugg M, Baksh S, Ballanyi K, Simmen T (2016) J Cell Biol
Abstract: The flux of Ca2+ from the endoplasmic reticulum (ER) to mitochondria regulates mitochondria metabolism. Within tumor tissue, mitochondria metabolism is frequently repressed, leading to chemotherapy resistance and increased growth of the tumor mass. Therefore, altered ER-mitochondria Ca2+ flux could be a cancer hallmark, but only a few regulatory proteins of this mechanism are currently known. One candidate is the redox-sensitive oxidoreductase TMX1 that is enriched on the mitochondria-associated membrane (MAM), the site of ER-mitochondria Ca2+ flux. Our findings demonstrate that cancer cells with low TMX1 exhibit increased ER Ca2+, accelerated cytosolic Ca2+ clearance, and reduced Ca2+ transfer to mitochondria. Thus, low levels of TMX1 reduce ER-mitochondria contacts, shift bioenergetics away from mitochondria, and accelerate tumor growth. For its role in intracellular ER-mitochondria Ca2+ flux, TMX1 requires its thioredoxin motif and palmitoylation to target to the MAM. As a thiol-based tumor suppressor, TMX1 increases mitochondrial ATP production and apoptosis progression. • Keywords: A375P human melanoma cells • Bioblast editor: Kandolf G • O2k-Network Lab: CA Edmonton Zaugg M
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Human, Mouse
Tissue;cell: Other cell lines, HeLa
Preparation: Intact cells, Permeabilized cells
Regulation: Calcium Coupling state: LEAK, ROUTINE, ET
HRR: Oxygraph-2k
2017-07
