Possible <scp>ATP</scp> trafficking by <scp>ATP</scp>‐shuttles in the olfactory cilia and glucose transfer across the olfactory mucosa

Acevedo, Claudia; Blanchard, Kris; Bacigalupo, Juan; Vergara, Cecilia

doi:10.1002/1873-3468.13346

Cited by 14 publications

(15 citation statements)

References 29 publications

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“…Sensorineural dysfunction is caused by damage of the ORNs and the olfactory nerve, impaired olfactory adaptation, and/or odorant transport. The supporting cells and the Bowman's glands are involved in olfactory adaptation and the neurotrophic and physical support of the OE (31)(32)(33). Thus, if the function of the supporting cells and the Bowman's glands was not certified by peer review) is the author/funder.…”

Section: Discussionmentioning

confidence: 99%

Understanding olfactory dysfunction in COVID-19: Expression of ACE2, TMPRSS2 and Furin in the nose and olfactory bulb in human and mice

Ueha

Kondo

Kagoya

et al. 2020

Preprint

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BackgroundAnosmia is a frequent symptom in coronavirus disease 2019 (COVID-19) patients that generally resolves within weeks. In contrast, the anosmia caused by other upper respiratory infections affects a small proportion of patients and may take months to resolve or never resolve. The mechanisms behind COVID-19-induced olfactory dysfunction remain unknown. Here, we address the unique pathophysiology of COVID-19-associated olfactory dysfunction.MethodsThe expression of ACE2 (virus binding receptor) and TMPRSS2 and Furin (host cell proteases facilitating virus entry) was examined in the nasal mucosa, composed of respiratory mucosa (RM), olfactory mucosa (OM), and olfactory bulb (OB) of mouse and human tissues using immunohistochemistry and gene analyses.ResultsCo-expression of ACE2, TMPRSS2, and Furin was observed in the RM and in the OM, especially in the supporting cells of the olfactory epithelium and the Bowman’s glands. Notably, the olfactory receptor neurons (ORNs) in the OM were positive for ACE2 but almost negative for TMPRSS2 and Furin. Cells in the OB expressed ACE2 strongly and Furin weakly, and did not express TMPRSS2. All three gene expressions were confirmed in the nasal mucosa and OB.ConclusionsACE2 was widely expressed in all tissues, whereas TMPRSS2 and Furin were expressed only in certain types of cells and were absent in the ORNs. These findings, together with clinical reports, suggest that COVID-19-related anosmia occurs mainly through sensorineural and central dysfunction and, to some extent, conductive olfactory dysfunction. The expression of ACE2, but not TMPRSS2 or Furin, in ORNs may explain the early recovery from anosmia.

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Section: Discussionmentioning

confidence: 99%

Understanding olfactory dysfunction in COVID-19: Expression of ACE2, TMPRSS2 and Furin in the nose and olfactory bulb in human and mice

Ueha

Kondo

Kagoya

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Rodent sustentacular cells have been ascribed myriad roles collectively referred to as ''supporting'': absorptive, detoxifying, metabolic, nourishing, phagocytic, physical, secretory, structural. One model, in rats, proposes that sustentacular cells take up glucose from blood vessels in the LP basally and secrete it into the mucus apically to fuel OSN cilia (Acevedo et al, 2019;Villar et al, 2017Villar et al, , 2021. A cytoarchitectonic study in rats illustrated the enwrapment of multiple OSN dendrites within the apical half of a single sustentacular cell (Liang, 2018.…”

Section: Infection Of Sustentacular Cellsmentioning

confidence: 99%

Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb

Khan

Yoo

Clijsters

et al. 2021

Cell

316

298

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Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected. ll

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“…Similar to primary cilia, mitochondria have a typical diameter of about 200 nm and cannot fit inside the ciliary structure. Thus, mitochondria must be located in close proximity to the cilium where they provide ATP, which can be equilibrated in the cilium using adenylate and creatine kinase shuttle ( Acevedo et al, 2019 ). More than 1,000 proteins are classified in the ciliary proteome, which combines results from high throughput proteomics, differential expression and comparative genomics studies (CiliaDB [ Arnaiz et al, 2009 ]).…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology

et al. 2022

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Primary cilia have recently emerged as cellular signaling organelles. Their homeostasis and function require a high amount of energy. However, how energy depletion and mitochondria impairment affect cilia have barely been addressed. We first studied the spatial relationship between a mitochondria subset in proximity to the cilium in vitro, finding similar mitochondrial activity measured as mitochondrial membrane potential compared with the cellular network. Next, using common primary cilia cell models and inhibitors of mitochondrial energy production, we found alterations in cilia number and/or length due to energy depletion and mitochondrial reactive oxygen species (ROS) overproduction. Finally, by using a mouse model of type 2 diabetes mellitus, we provided in vivo evidence that cilia morphology is impaired in diabetic nephropathy, which is characterized by ROS overproduction and impaired mitochondrial metabolism. In conclusion, we showed that energy imbalance and mitochondrial ROS affect cilia morphology and number, indicating that conditions characterized by mitochondria and radicals imbalances might lead to ciliary impairment.

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Possible ATP trafficking by ATP‐shuttles in the olfactory cilia and glucose transfer across the olfactory mucosa

Cited by 14 publications

References 29 publications

Understanding olfactory dysfunction in COVID-19: Expression of ACE2, TMPRSS2 and Furin in the nose and olfactory bulb in human and mice

Understanding olfactory dysfunction in COVID-19: Expression of ACE2, TMPRSS2 and Furin in the nose and olfactory bulb in human and mice

Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb

Mitochondrial impairment and intracellular reactive oxygen species alter primary cilia morphology

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