Ratiometric measurement of MAM Ca2+ dynamics using a modified CalfluxVTN

Cho, Eunbyul; Woo, Youngsik; Suh, Yeongjun; Suh, Bo Kyoung; Kim, Soo Jeong; Nhung, Truong Thi My; Yoo, Jin Yeong; Nghi, Tran Diem; Mun, Dong Jin

doi:10.1038/s41467-023-39343-2

Cited by 7 publications

(6 citation statements)

References 76 publications

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“…Recent studies have shown that in addition to their distinct functions in the cell, the mitochondria and endoplasmic reticulum (ER) interact both physically and functionally, which has attracted significant study interest in recent years . Mitochondria-associated ER membranes (MAMs) are the contact sites between the ER membrane and the mitochondria membrane, which can mediate Ca 2+ and metabolite transfer between mitochondria and ER . MAMs regulate various cell processes through signaling events including Ca 2+ homeostasis, inflammatory response, oxidative stress, or apoptosis .…”

Section: Introductionmentioning

confidence: 99%

Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum–Mitochondria Interaction

Zhao,

Chang,

Ren

et al. 2024

J. Agric. Food Chem.

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phthalate (DEHP), as the most common phthalate, has been extensively used as a plasticizer to improve the plasticity of agricultural products, which pose severe harm to human health. Mitochondrial dynamics and endoplasmic reticulum (ER) homeostasis are indispensable for maintaining mitochondria-associated ER membrane (MAM) integrity. In this study, we aimed to explore the effect of DEHP on the nervous system and its association with the ER−mitochondria interaction. Here, we showed that DEHP caused morphological changes, motor deficits, cognitive impairments, and blood−brain barrier disruption in the brain. DEHP triggered ER stress, which is mainly mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) signaling. Moreover, DEHP-induced mitofusin-2 (Mfn2) downregulation results in imbalance of the mitochondrial dynamics. Interestingly, DEHP exposure impaired MAMs by inhibiting the Mfn2-PERK interaction. Above all, this study elucidates the disruption of the Mfn2-PERK axis-mediated ER−mitochondria interaction as a phthalate-induced neurotoxicity that could be potentially developed as a novel therapy for neurological diseases.

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Section: Introductionmentioning

confidence: 99%

Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum–Mitochondria Interaction

Zhao,

Chang,

Ren

et al. 2024

J. Agric. Food Chem.

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“…Nor can we rule out the possibility that ER depletion, via TRPV1 activation, is responsible for both phenomena. To complicate matters further, the recently developed MAM Ca 2+ probe, CalfluxVTN, has taught us that the two may be unrelated [ 71 ]. In other words, the increased MAM Ca 2+ levels are not necessarily associated with structural changes in MAMs [ 71 ].…”

Section: Resultsmentioning

confidence: 99%

“…To complicate matters further, the recently developed MAM Ca 2+ probe, CalfluxVTN, has taught us that the two may be unrelated [ 71 ]. In other words, the increased MAM Ca 2+ levels are not necessarily associated with structural changes in MAMs [ 71 ]. This puzzling issue needs further investigation.…”

Section: Resultsmentioning

confidence: 99%

TRPV1 Channels Are New Players in the Reticulum–Mitochondria Ca2+ Coupling in a Rat Cardiomyoblast Cell Line

Tessier,

Ducrozet,

Dia

et al. 2023

Cells

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The Ca2+ release in microdomains formed by intercompartmental contacts, such as mitochondria-associated endoplasmic reticulum membranes (MAMs), encodes a signal that contributes to Ca2+ homeostasis and cell fate control. However, the composition and function of MAMs remain to be fully defined. Here, we focused on the transient receptor potential vanilloid 1 (TRPV1), a Ca2+-permeable ion channel and a polymodal nociceptor. We found TRPV1 channels in the reticular membrane, including some at MAMs, in a rat cardiomyoblast cell line (SV40-transformed H9c2) by Western blotting, immunostaining, cell fractionation, and proximity ligation assay. We used chemical and genetic probes to perform Ca2+ imaging in four cellular compartments: the endoplasmic reticulum (ER), cytoplasm, mitochondrial matrix, and mitochondrial surface. Our results showed that the ER Ca2+ released through TRPV1 channels is detected at the mitochondrial outer membrane and transferred to the mitochondria. Finally, we observed that prolonged TRPV1 modulation for 30 min alters the intracellular Ca2+ equilibrium and influences the MAM structure or the hypoxia/reoxygenation-induced cell death. Thus, our study provides the first evidence that TRPV1 channels contribute to MAM Ca2+ exchanges.

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“…Improved developments in genetically encoded calcium indicators (GECIs), such as fluorescence resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET), have better enabled the steady-state assessment of Ca 2+ concentration [ 96 , 97 ]. Recently, MAM-specific Ca 2+ sensors using bimolecular fluorescence complementation (BiFC) technology have been developed that allow for specific investigations of Ca 2+ dynamics at the MAM [ 98 ].…”

Section: Mitochondria-associated Er Membranes (Mams)mentioning

confidence: 99%

A-Syn(ful) MAM: A Fresh Perspective on a Converging Domain in Parkinson’s Disease

Barbuti

2024

IJMS

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Parkinson’s disease (PD) is a disease of an unknown origin. Despite that, decades of research have provided considerable evidence that alpha-synuclein (αSyn) is central to the pathogenesis of disease. Mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are functional domains formed at contact sites between the ER and mitochondria, with a well-established function of MAMs being the control of lipid homeostasis within the cell. Additionally, there are numerous proteins localized or enriched at MAMs that have regulatory roles in several different molecular signaling pathways required for cellular homeostasis, such as autophagy and neuroinflammation. Alterations in several of these signaling pathways that are functionally associated with MAMs are found in PD. Taken together with studies that find αSyn localized at MAMs, this has implicated MAM (dys)function as a converging domain relevant to PD. This review will highlight the many functions of MAMs and provide an overview of the literature that finds αSyn, in addition to several other PD-related proteins, localized there. This review will also detail the direct interaction of αSyn and αSyn-interacting partners with specific MAM-resident proteins. In addition, recent studies exploring new methods to investigate MAMs will be discussed, along with some of the controversies regarding αSyn, including its several conformations and subcellular localizations. The goal of this review is to highlight and provide insight on a domain that is incompletely understood and, from a PD perspective, highlight those complex interactions that may hold the key to understanding the pathomechanisms underlying PD, which may lead to the targeted development of new therapeutic strategies.

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Ratiometric measurement of MAM Ca2+ dynamics using a modified CalfluxVTN

Cited by 7 publications

References 76 publications

Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum–Mitochondria Interaction

Phthalates Induce Neurotoxicity by Disrupting the Mfn2-PERK Axis-Mediated Endoplasmic Reticulum–Mitochondria Interaction

TRPV1 Channels Are New Players in the Reticulum–Mitochondria Ca2+ Coupling in a Rat Cardiomyoblast Cell Line

A-Syn(ful) MAM: A Fresh Perspective on a Converging Domain in Parkinson’s Disease

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