Biomaterial Database

Mitochondria control store-operated Ca2+ entry through Na+ and redox signals. 2017

Tsipi Ben-Kasus Nissim, and Xuexin Zhang, and Assaf Elazar, and Soumitra Roy, and Judith A Stolwijk, and Yandong Zhou, and Rajender K Motiani, and Maxime Gueguinou, and Nadine Hempel, and Michal Hershfinkel, and Donald L Gill, and Mohamed Trebak, and Israel Sekler

The Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Mitochondria exert important control over plasma membrane (PM) Orai1 channels mediating store-operated Ca2+ entry (SOCE). Although the sensing of endoplasmic reticulum (ER) Ca2+ stores by STIM proteins and coupling to Orai1 channels is well understood, how mitochondria communicate with Orai1 channels to regulate SOCE activation remains elusive. Here, we reveal that SOCE is accompanied by a rise in cytosolic Na+ that is critical in activating the mitochondrial Na+/Ca2+ exchanger (NCLX) causing enhanced mitochondrial Na+ uptake and Ca2+ efflux. Omission of extracellular Na+ prevents the cytosolic Na+ rise, inhibits NCLX activity, and impairs SOCE and Orai1 channel current. We show further that SOCE activates a mitochondrial redox transient which is dependent on NCLX and is required for preventing Orai1 inactivation through oxidation of a critical cysteine (Cys195) in the third transmembrane helix of Orai1. We show that mitochondrial targeting of catalase is sufficient to rescue redox transients, SOCE, and Orai1 currents in NCLX-deficient cells. Our findings identify a hitherto unknown NCLX-mediated pathway that coordinates Na+ and Ca2+ signals to effect mitochondrial redox control over SOCE.

UI	MeSH Term	Description	Entries
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D010084	Oxidation-Reduction	A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).	Redox,Oxidation Reduction
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071740	ORAI1 Protein	The pore-forming subunit of calcium release activated calcium channels. It is activated by STROMAL INTERACTION MOLECULE 1 upon intracellular calcium depletion.	Calcium Release-Activated Calcium Channel Protein 1,ORAI Calcium Release-Activated Calcium Modulator 1,Calcium Release Activated Calcium Channel Protein 1,ORAI Calcium Release Activated Calcium Modulator 1
D012964	Sodium	A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.	Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D019831	Sodium-Calcium Exchanger	An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart.	Ca(2+)-Na(+) Exchanger,Calcium-Sodium Carrier,Calcium-Sodium Exchanger,Na(+)-Ca(2+) Exchanger,Sodium-Calcium Carrier,Ca(2+)-Na(+) Antiporter,Calcium-Sodium Antiporter,Na(+)-Ca(2+) Antiporter,Sodium-Calcium Antiporter,Antiporter, Calcium-Sodium,Antiporter, Sodium-Calcium,Calcium Sodium Antiporter,Calcium Sodium Carrier,Calcium Sodium Exchanger,Carrier, Calcium-Sodium,Carrier, Sodium-Calcium,Exchanger, Calcium-Sodium,Exchanger, Sodium-Calcium,Sodium Calcium Antiporter,Sodium Calcium Carrier,Sodium Calcium Exchanger
D024101	Mitochondrial Proteins	Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.	Proteins, Mitochondrial,Mitochondrial Protein,Protein, Mitochondrial