Raturi 2016 J Cell Biol

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Publications in the MiPMap
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.

» PMID: 27502484 Open Access

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