Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Naghdi, S; Waideck-Weiermair, M; Fertschai, I; Poteser, M; Graier, WF; Malli, R.
Mitochondrial Ca2+ uptake and not mitochondrial motility is required for STIM1-Orai1-dependent store-operated Ca2+ entry.
J CELL SCI. 2010; 123(Pt 15): 2553-2564.
Doi: 10.1242/jcs.070151
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- Führende Autor*innen der Med Uni Graz
- Malli Roland
- Naghdi Shamim
- Co-Autor*innen der Med Uni Graz
- Fertschai Ismene
- Graier Wolfgang
- Poteser Michael
- Waldeck-Weiermair Markus
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Calcium - metabolism
- Calcium Channels - genetics Calcium Channels - metabolism
- Cell Line -
- Humans -
- Membrane Proteins - genetics Membrane Proteins - metabolism
- Microscopy, Confocal -
- Mitochondria - metabolism
- Neoplasm Proteins - genetics Neoplasm Proteins - metabolism
- Reverse Transcriptase Polymerase Chain Reaction -
- Find related publications in this database (Keywords)
- Capacitative Ca2+ entry
- ER Ca2+ release
- Mitochondrial Ca2+ uniporter
- Mitochondrial motility
- NCXmito
- Pericam
- SOCE
- Stromal interacting molecule
- Calcium