Ca2+ signaling at membrane contact sites

Hofer, Aldebaran M.

doi:10.1016/j.ceca.2015.07.002

Cited by 3 publications

(3 citation statements)

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“…ATX‐2/Ataxin‐2/DAtx2 could function to mediate and maintain the structure and function of the cortical ER, which is rich in RNA‐binding proteins . Cortical ER also contacts the plasma membrane at membrane contact sites (MCSs), which are unique sites shown to regulate cellular calcium levels . Depletion of ATX‐2/DAtx2 could lead to altered calcium homeostasis within the cell, contributing to delays in the cell cycle, such as the delay during the anaphase‐telophase transition we previously observed .…”

Section: Resultsmentioning

confidence: 91%

Conserved role for Ataxin‐2 in mediating endoplasmic reticulum dynamics

Castillo

Gnazzo

Turpin

et al. 2019

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Ataxin-2, a conserved RNA-binding protein, is implicated in the late-onset neurodegenerative disease Spinocerebellar ataxia type-2 (SCA2). SCA2 is characterized by shrunken dendritic arbors and torpedo-like axons within the Purkinje neurons of the cerebellum. Torpedo-like axons have been described to contain displaced endoplasmic reticulum (ER) in the periphery of the cell; however, the role of Ataxin-2 in mediating ER function in SCA2 is unclear. We utilized the Caenorhabditis elegans and Drosophila homologs of Ataxin-2 (ATX-2 and DAtx2, respectively) to determine the role of Ataxin-2 in ER function and dynamics in embryos and neurons. Loss of ATX-2 and DAtx2 resulted in collapse of the ER in dividing embryonic cells and germline, and ultrastructure analysis revealed unique spherical stacks of ER in mature oocytes and fragmented and truncated ER tubules in the embryo. ATX-2 and DAtx2 reside in puncta adjacent to the ER in both C. elegans and Drosophila embryos. Lastly, depletion of DAtx2 in cultured Drosophila neurons recapitulated the shrunken dendritic arbor phenotype of SCA2. ER morphology and dynamics were severely disrupted in these neurons. Taken together, we provide evidence that Ataxin-2 plays an evolutionary conserved role in ER dynamics and morphology in C. elegans and Drosophila embryos during development and in fly neurons, suggesting a possible SCA2 disease mechanism.

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Section: Resultsmentioning

confidence: 91%

Conserved role for Ataxin‐2 in mediating endoplasmic reticulum dynamics

Castillo

Gnazzo

Turpin

et al. 2019

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“…mitochondria | optogenetic | mitochondrial membrane potential | Ca 2+ signaling M itochondria play a critical role in all nucleated eukaryotic cells by producing ATP, actively participating in intracellular Ca 2+ signaling, and modulating cell viability (1)(2)(3). All these functions are driven by the H + electrochemical gradient (ΔμH + ) across the inner mitochondrial membrane (IMM), which is generated by the extrusion of protons from the mitochondrial matrix through respiratory chain complexes (4).…”

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confidence: 99%

Optogenetic control of mitochondrial metabolism and Ca ²⁺ signaling by mitochondria-targeted opsins

Tkatch

Greotti

Baranauskas

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Key mitochondrial functions such as ATP production, Ca uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH) across the inner membrane. Although several drugs can modulate ΔμH, their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψ) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca dynamics, and respiratory metabolism. By directly modulating Δψ, the mitochondria-targeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.

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“…M itochondria play a critical role in all nucleated eukaryotic cells by producing ATP, actively participating in intracellular Ca 2+ signaling, and modulating cell viability (1)(2)(3). All these functions are driven by the H + electrochemical gradient (ΔμH + ) across the inner mitochondrial membrane (IMM), which is generated by the extrusion of protons from the mitochondrial matrix through respiratory chain complexes (4).…”

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confidence: 99%

Faculty Opinions recommendation of Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

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2020

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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Key mitochondrial functions such as ATP production, Ca 2+ uptake and release, and substrate accumulation depend on the proton electrochemical gradient (ΔμH + ) across the inner membrane. Although several drugs can modulate ΔμH + , their effects are hardly reversible, and lack cellular specificity and spatial resolution. Although channelrhodopsins are widely used to modulate the plasma membrane potential of excitable cells, mitochondria have thus far eluded optogenetic control. Here we describe a toolkit of optometabolic constructs based on selective targeting of channelrhodopsins with distinct functional properties to the inner mitochondrial membrane of intact cells. We show that our strategy enables a light-dependent control of the mitochondrial membrane potential (Δψ m ) and coupled mitochondrial functions such as ATP synthesis by oxidative phosphorylation, Ca 2+ dynamics, and respiratory metabolism. By directly modulating Δψ m , the mitochondriatargeted opsins were used to control complex physiological processes such as spontaneous beats in cardiac myocytes and glucose-dependent ATP increase in pancreatic β-cells. Furthermore, our optometabolic tools allow modulation of mitochondrial functions in single cells and defined cell regions.

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Ca2+ signaling at membrane contact sites

Cited by 3 publications

References 10 publications

Conserved role for Ataxin‐2 in mediating endoplasmic reticulum dynamics

Conserved role for Ataxin‐2 in mediating endoplasmic reticulum dynamics

Optogenetic control of mitochondrial metabolism and Ca ²⁺ signaling by mitochondria-targeted opsins

Faculty Opinions recommendation of Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

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Ca2+ signaling at membrane contact sites

Cited by 3 publications

References 10 publications

Conserved role for Ataxin‐2 in mediating endoplasmic reticulum dynamics

Conserved role for Ataxin‐2 in mediating endoplasmic reticulum dynamics

Optogenetic control of mitochondrial metabolism and Ca 2+ signaling by mitochondria-targeted opsins

Faculty Opinions recommendation of Optogenetic control of mitochondrial metabolism and Ca2+ signaling by mitochondria-targeted opsins.

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Product

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Optogenetic control of mitochondrial metabolism and Ca ²⁺ signaling by mitochondria-targeted opsins