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Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry.
J Cell Sci. 2010 Aug 01; 123(Pt 15):2553-64.JC

Abstract

Store-operated Ca(2+) entry (SOCE) is established by formation of subplasmalemmal clusters of the endoplasmic reticulum (ER) protein, stromal interacting molecule 1 (STIM1) upon ER Ca(2+) depletion. Thereby, STIM1 couples to plasma membrane channels such as Orai1. Thus, a close proximity of ER domains to the plasma membrane is a prerequisite for SOCE activation, challenging the concept of local Ca(2+) buffering by mitochondria as being essential for SOCE. This study assesses the impact of mitochondrial Ca(2+) handling and motility on STIM1-Orai1-dependent SOCE. High-resolution microscopy showed only 10% of subplasmalemmal STIM1 clusters to be colocalized with mitochondria. Impairments of mitochondrial Ca(2+) handling by inhibition of mitochondrial Na(+)-Ca(2+) exchanger (NCX(mito)) or depolarization only partially suppressed Ca(2+) entry in cells overexpressing STIM1-Orai1. However, SOCE was completely abolished when both NCX(mito) was inhibited and the inner mitochondrial membrane was depolarized, in STIM1- and Orai1-overexpressing cells. Immobilization of mitochondria by expression of mAKAP-RFP-CAAX, a construct that physically links mitochondria to the plasma membrane, affected the Ca(2+) handling of the organelles but not the activity of SOCE. Our observations indicate that mitochondrial Ca(2+) uptake, including reversal of NCX(mito), is fundamental for STIM1-Orai1-dependent SOCE, whereas the proximity of mitochondria to STIM1-Orai1 SOCE units and their motility is not required.

Authors+Show Affiliations

Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, 8010 Graz, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20587595

Citation

Naghdi, Shamim, et al. "Mitochondrial Ca2+ Uptake and Not Mitochondrial Motility Is Required for STIM1-Orai1-dependent Store-operated Ca2+ Entry." Journal of Cell Science, vol. 123, no. Pt 15, 2010, pp. 2553-64.
Naghdi S, Waldeck-Weiermair M, Fertschai I, et al. Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry. J Cell Sci. 2010;123(Pt 15):2553-64.
Naghdi, S., Waldeck-Weiermair, M., Fertschai, I., Poteser, M., Graier, W. F., & Malli, R. (2010). Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry. Journal of Cell Science, 123(Pt 15), 2553-64. https://doi.org/10.1242/jcs.070151
Naghdi S, et al. Mitochondrial Ca2+ Uptake and Not Mitochondrial Motility Is Required for STIM1-Orai1-dependent Store-operated Ca2+ Entry. J Cell Sci. 2010 Aug 1;123(Pt 15):2553-64. PubMed PMID: 20587595.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry. AU - Naghdi,Shamim, AU - Waldeck-Weiermair,Markus, AU - Fertschai,Ismene, AU - Poteser,Michael, AU - Graier,Wolfgang F, AU - Malli,Roland, Y1 - 2010/06/29/ PY - 2010/7/1/entrez PY - 2010/7/1/pubmed PY - 2011/1/28/medline SP - 2553 EP - 64 JF - Journal of cell science JO - J Cell Sci VL - 123 IS - Pt 15 N2 - Store-operated Ca(2+) entry (SOCE) is established by formation of subplasmalemmal clusters of the endoplasmic reticulum (ER) protein, stromal interacting molecule 1 (STIM1) upon ER Ca(2+) depletion. Thereby, STIM1 couples to plasma membrane channels such as Orai1. Thus, a close proximity of ER domains to the plasma membrane is a prerequisite for SOCE activation, challenging the concept of local Ca(2+) buffering by mitochondria as being essential for SOCE. This study assesses the impact of mitochondrial Ca(2+) handling and motility on STIM1-Orai1-dependent SOCE. High-resolution microscopy showed only 10% of subplasmalemmal STIM1 clusters to be colocalized with mitochondria. Impairments of mitochondrial Ca(2+) handling by inhibition of mitochondrial Na(+)-Ca(2+) exchanger (NCX(mito)) or depolarization only partially suppressed Ca(2+) entry in cells overexpressing STIM1-Orai1. However, SOCE was completely abolished when both NCX(mito) was inhibited and the inner mitochondrial membrane was depolarized, in STIM1- and Orai1-overexpressing cells. Immobilization of mitochondria by expression of mAKAP-RFP-CAAX, a construct that physically links mitochondria to the plasma membrane, affected the Ca(2+) handling of the organelles but not the activity of SOCE. Our observations indicate that mitochondrial Ca(2+) uptake, including reversal of NCX(mito), is fundamental for STIM1-Orai1-dependent SOCE, whereas the proximity of mitochondria to STIM1-Orai1 SOCE units and their motility is not required. SN - 1477-9137 UR - https://www.unboundmedicine.com/medline/citation/20587595/Mitochondrial_Ca2+_uptake_and_not_mitochondrial_motility_is_required_for_STIM1_Orai1_dependent_store_operated_Ca2+_entry_ L2 - http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=20587595 DB - PRIME DP - Unbound Medicine ER -