Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11

Sorrentino, Ilaria; Galli, M; Medraño-Fernández, Iria; Sitia, Roberto

doi:10.1016/j.redox.2022.102410

Cited by 17 publications

(7 citation statements)

References 66 publications

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“…This process coincides with, and appears to be dependent on, increased mitochondria‐ER MCS. [ 89 ] One possibility, which would be interesting to explore, is that the efflux of H 2 O 2 from the mitochondria to the ER through AQP11 could be mediated by direct redox modulation of tether proteins. [ 80,81 ]…”

Section: Regulation Of Mcs By Redox Signallingmentioning

confidence: 99%

“…This process coincides with, and appears to be dependent on, increased mitochondria-ER MCS. [89] One possibility, which would be interesting to explore, is that the efflux of H 2 O 2 from the mitochondria to the ER through AQP11 could be mediated by direct redox modulation of tether proteins. [80,81] As ROS, often in the form of H 2 O 2 , is generated as part of numerous biochemical reactions, for example during beta-oxidation of VLCFAs in peroxisomes, linking ROS flux to the control of MCS allows the possibility to couple the extent of lipid exchange at MCS to the level of ROS being produced by a particular organelle.…”

Section: Redox Regulation At Mitochondria-er Mcs Is An Example Of Howmentioning

confidence: 99%

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Controlling contacts—Molecular mechanisms to regulate organelle membrane tethering

et al. 2022

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In recent years, membrane contact sites (MCS), which mediate interactions between virtually all subcellular organelles, have been extensively characterized and shown to be essential for intracellular communication. In this review essay, we focus on an emerging topic: the regulation of MCS. Focusing on the tether proteins themselves, we discuss some of the known mechanisms which can control organelle tethering events and identify apparent common regulatory hubs, such as the VAP interface at the endoplasmic reticulum (ER). We also highlight several currently hypothetical concepts, including the idea of tether oligomerization and redox regulation playing a role in MCS formation. We identify gaps in our current understanding, such as the identity of the majority of kinases/phosphatases involved in tether modification and conclude that a holistic approach-incorporating the formation of multiple MCS, regulated by interconnected regulatory modulators-may be required to fully appreciate the true complexity of these fascinating intracellular communication systems.

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Section: Regulation Of Mcs By Redox Signallingmentioning

confidence: 99%

Section: Redox Regulation At Mitochondria-er Mcs Is An Example Of Howmentioning

confidence: 99%

Controlling contacts—Molecular mechanisms to regulate organelle membrane tethering

et al. 2022

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“…We propose that upregulation of H 2 O 2 during RT cause mitochondrial respiratory impairment which subsequently mediates EV production with mitochondria as a cargo to maintain mitochondrial quality control by removing damaged mitochondria or deliver mitochondrial contents to recipient cells [ 63 ]. More importantly, alteration of mitochondrial respiratory function could further promote mitochondrial H 2 O 2 production which can be transported across mitochondrial membrane to endoplasmic reticulum via aquaporin 11, allowing redox signal conduct in cytoplasm [ 66 ] such as activation of calmodulin-dependent protein kinase kinase (CaMKK) [ 67 ], which is responsible for MVE formation [ 64 , 68 ]. Please note, in addition to mitochondria or mitochondrial proteins as cargo, RT-derived EVs could carry miRNA, DNA, cytokines, and other transcription factors; which are not being discussed since they are beyond the scope of this study.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Peroxide Promotes the Production of Radiation-Derived EVs Containing Mitochondrial Proteins

Miller

Zhao

et al. 2022

Antioxidants

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In spite of extensive successes, cancer recurrence after radiation treatment (RT) remains one of the significant challenges in the cure of localized prostate cancer (PCa). This study focuses on elucidating a novel adaptive response to RT that could contribute to cancer recurrence. Here, we used PC3 cell line, an adenocarcinoma from a bone metastasis and radio-resistant clone 695 cell line, which survived after total radiation dose of 66 Gy (2 Gy × 33) and subsequently regrew in nude mice after exposure to fractionated radiation at 10 Gy (2 Gy × 5). Clone 695 cells not only showed an increase in surviving fraction post-radiation but also an increase in hydrogen peroxide (H2O2) production when compared to PC3 cells. At the single cell level, confocal microscope images coupled with IMARIS rendering software demonstrate an increase in mitochondrial mass and membrane potential in clone 695 cells. Utilizing the Seahorse XF96 instrument to investigate mitochondrial respiration, clone 695 cells demonstrated a higher basal Oxygen Consumption Rate (OCR), ATP-linked OCR, and proton leak compared to PC3 cells. The elevation of mitochondrial function in clone 695 cells is accompanied by an increase in mitochondrial H2O2 production. These data suggest that H2O2 could reprogram PCa’s mitochondrial homeostasis, which allows the cancer to survive and regrow after RT. Upon exposure to RT, in addition to ROS production, we found that RT induces the release of extracellular vesicles (EVs) from PC3 cells (p < 0.05). Importantly, adding H2O2 to PC3 cells promotes EVs production in a dose-dependent manner and pre-treatment with polyethylene glycol-Catalase mitigates H2O2-mediated EV production. Both RT-derived EVs and H2O2-derived EVs carried higher levels of mitochondrial antioxidant proteins including, Peroxiredoxin 3, Glutathione Peroxidase 4 as well as mitochondrial-associated oxidative phosphorylation proteins. Significantly, adding isolated functional mitochondria 24 h prior to RT shows a significant increase in surviving fractions of PC3 cells (p < 0.05). Together, our findings reveal that H2O2 promotes the production of EVs carrying mitochondrial proteins and that functional mitochondria enhance cancer survival after RT.

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“…In mammals, AQPs are subdivided into classical AQPs (AQP0, 1, 2, 4, 5, 6 and 8), which mainly pass water, aquaglyceroporins (AQP3, 7, 9 and 10), which pass water and small solutes including glycerol and urea, and the unorthodox AQPs (AQP11 and 12) with yet unknown function, undefined permeability and low sequence homology [41][42][43][44]. However, unorthodox AQP11 has been proposed to facilitate the transport of glycerol and H 2 O 2 [45][46].…”

Section: Aquaporins In Salivary Fluid Secretionmentioning

confidence: 99%

Molecular mechanisms of saliva secretion and hyposecretion

Song,

Chung,

Kim

2024

European J Oral Sciences

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The exocrine salivary gland secretes saliva, a fundamental body component to maintain oral homeostasis. Saliva is composed of water, ions, and proteins such as amylase, mucins, and immunoglobulins that play essential roles in the digestion of food, lubrication, and prevention of dental caries and periodontitis. An increasing number of people experience saliva hyposecretion due to aging, medications, Sjögren's syndrome, and radiation therapy for head and neck cancer. However, current treatments are mostly limited to temporary symptomatic relief. This review explores the molecular mechanisms underlying saliva secretion and hyposecretion to provide insight into putative therapeutic targets for treatment. Proteins implicated in saliva secretion pathways, including Ca2+‐signaling proteins, aquaporins, soluble N‐ethylmaleimide‐sensitive factor attachment protein receptors, and tight junctions, are aberrantly expressed and localized in patients with saliva hyposecretion, such as Sjögren's syndrome. Analysis of studies on the mechanisms of saliva secretion and hyposecretion suggests that crosstalk between fluid and protein secretory pathways via Ca2+/protein kinase C and cAMP/protein kinase A regulates saliva secretion. Impaired crosstalk between the two secretory pathways may contribute to saliva hyposecretion. Future research into the detailed regulatory mechanisms of saliva secretion and hyposecretion may provide information to define novel targets and generate therapeutic strategies for saliva hyposecretion.

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Transfer of H2O2 from Mitochondria to the endoplasmic reticulum via Aquaporin-11

Cited by 17 publications

References 66 publications

Controlling contacts—Molecular mechanisms to regulate organelle membrane tethering

Controlling contacts—Molecular mechanisms to regulate organelle membrane tethering

Hydrogen Peroxide Promotes the Production of Radiation-Derived EVs Containing Mitochondrial Proteins

Molecular mechanisms of saliva secretion and hyposecretion

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