期刊
CELL CALCIUM
卷 72, 期 -, 页码 62-69出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2018.03.001
关键词
ORP5; ORP8; Caveolae; Mitochondria; Endoplasmic reticulum; Calcium
类别
资金
- Academy of Finland [285223]
- Sigrid Juselius Foundation
- Finnish Foundation for Cardiovascular Research
- Magnus Ehrnrooths stiftelse
- Liv och Halsa Foundation
- Finsk-Norska medicinska stiftelsen
- Tor, Joe och Pentti Borgs Minnesfond
- Oscar Oflunds stiftelse
- Waldemar Von Frenckells stiftelse
- K. Albin Johanssons stiftelse
- Ida Montins stiftelse
- Svenska Kulturfonden
Oxysterol-binding protein related-protein 5 and 8 (ORP5/8) localize to the membrane contact sites (MCS) of the endoplasmic reticulum (ER) and the mitochondria, as well as to the ER-plasma membrane (PM) MCS. The MCS are emerging as important regulators of cell signaling events, including calcium (Ca2+) signaling. ORP5/8 have been shown to interact with phosphatidylinositol-4,5-bisphosphate (PIP2) in the PM, and to modulate mitochondrial respiration and morphology. PIP2 is the direct precursor of inositol trisphosphate (IP3), a key second messenger responsible for Ca2+-release from the intracellular Ca2+ stores. Further, mitochondrial respiration is linked to Ca2+ transfer from the ER to the mitochondria. Hence, we asked whether ORP5/8 would affect Ca2+ signaling in these cell compartments, and employed genetically engineered aequorin Ca2+ probes to investigate the effect of ORP5/8 in the regulation of mitochondrial and caveolar Ca2+. Our results show that ORP5/8 overexpression leads to increased mitochondrial matrix Ca2+ as well as to increased Ca2+ concentration at the caveolar subdomains of the PM during histamine stimulation, while having no effect on the cytoplasmic Ca2+. Also, we found that ORP5/8 overexpression increases cell proliferation. Our results show that ORP5/8 regulate Ca2+ signaling at specific MCS foci. These local ORP5/8-mediated Ca2+ signaling events are likely to play roles in processes such as mitochondrial respiration and cell proliferation.
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