Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection
Abstract Retinal ganglion cells are highly metabolically active requiring strictly regulated metabolism and functional mitochondria to keep ATP levels in physiological range. Imbalances in metabolism and mitochondrial mechanisms can be sufficient to induce a depletion of ATP, thus altering retinal g...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-023-01642-6 |
| _version_ | 1797451140778950656 |
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| author | Alessio Canovai James R. Tribble Melissa Jöe Daniela Y. Westerlund Rosario Amato Ian A. Trounce Massimo Dal Monte Pete A. Williams |
| author_facet | Alessio Canovai James R. Tribble Melissa Jöe Daniela Y. Westerlund Rosario Amato Ian A. Trounce Massimo Dal Monte Pete A. Williams |
| author_sort | Alessio Canovai |
| collection | DOAJ |
| description | Abstract Retinal ganglion cells are highly metabolically active requiring strictly regulated metabolism and functional mitochondria to keep ATP levels in physiological range. Imbalances in metabolism and mitochondrial mechanisms can be sufficient to induce a depletion of ATP, thus altering retinal ganglion cell viability and increasing cell susceptibility to death under stress. Altered metabolism and mitochondrial abnormalities have been demonstrated early in many optic neuropathies, including glaucoma, autosomal dominant optic atrophy, and Leber hereditary optic neuropathy. Pyrroloquinoline quinone (PQQ) is a quinone cofactor and is reported to have numerous effects on cellular and mitochondrial metabolism. However, the reported effects are highly context-dependent, indicating the need to study the mechanism of PQQ in specific systems. We investigated whether PQQ had a neuroprotective effect under different retinal ganglion cell stresses and assessed the effect of PQQ on metabolic and mitochondrial processes in cortical neuron and retinal ganglion cell specific contexts. We demonstrated that PQQ is neuroprotective in two models of retinal ganglion cell degeneration. We identified an increased ATP content in healthy retinal ganglion cell-related contexts both in in vitro and in vivo models. Although PQQ administration resulted in a moderate effect on mitochondrial biogenesis and content, a metabolic variation in non-diseased retinal ganglion cell-related tissues was identified after PQQ treatment. These results suggest the potential of PQQ as a novel neuroprotectant against retinal ganglion cell death. |
| first_indexed | 2024-03-09T14:50:32Z |
| format | Article |
| id | doaj.art-9b0fb1fc29404f1ebda176ae9e7a591f |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-09T14:50:32Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-9b0fb1fc29404f1ebda176ae9e7a591f2023-11-26T14:31:58ZengBMCActa Neuropathologica Communications2051-59602023-09-0111112310.1186/s40478-023-01642-6Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotectionAlessio Canovai0James R. Tribble1Melissa Jöe2Daniela Y. Westerlund3Rosario Amato4Ian A. Trounce5Massimo Dal Monte6Pete A. Williams7Division of Eye and Vision, Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska InstitutetDivision of Eye and Vision, Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska InstitutetDivision of Eye and Vision, Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska InstitutetDivision of Eye and Vision, Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska InstitutetDepartment of Biology, University of PisaDepartment of Surgery, Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Ophthalmology, University of MelbourneDepartment of Biology, University of PisaDivision of Eye and Vision, Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska InstitutetAbstract Retinal ganglion cells are highly metabolically active requiring strictly regulated metabolism and functional mitochondria to keep ATP levels in physiological range. Imbalances in metabolism and mitochondrial mechanisms can be sufficient to induce a depletion of ATP, thus altering retinal ganglion cell viability and increasing cell susceptibility to death under stress. Altered metabolism and mitochondrial abnormalities have been demonstrated early in many optic neuropathies, including glaucoma, autosomal dominant optic atrophy, and Leber hereditary optic neuropathy. Pyrroloquinoline quinone (PQQ) is a quinone cofactor and is reported to have numerous effects on cellular and mitochondrial metabolism. However, the reported effects are highly context-dependent, indicating the need to study the mechanism of PQQ in specific systems. We investigated whether PQQ had a neuroprotective effect under different retinal ganglion cell stresses and assessed the effect of PQQ on metabolic and mitochondrial processes in cortical neuron and retinal ganglion cell specific contexts. We demonstrated that PQQ is neuroprotective in two models of retinal ganglion cell degeneration. We identified an increased ATP content in healthy retinal ganglion cell-related contexts both in in vitro and in vivo models. Although PQQ administration resulted in a moderate effect on mitochondrial biogenesis and content, a metabolic variation in non-diseased retinal ganglion cell-related tissues was identified after PQQ treatment. These results suggest the potential of PQQ as a novel neuroprotectant against retinal ganglion cell death.https://doi.org/10.1186/s40478-023-01642-6Pyrroloquinoline quinone (PQQ)MitochondriaMetabolismMetabolomicsATPRetinal ganglion cell |
| spellingShingle | Alessio Canovai James R. Tribble Melissa Jöe Daniela Y. Westerlund Rosario Amato Ian A. Trounce Massimo Dal Monte Pete A. Williams Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection Acta Neuropathologica Communications Pyrroloquinoline quinone (PQQ) Mitochondria Metabolism Metabolomics ATP Retinal ganglion cell |
| title | Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection |
| title_full | Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection |
| title_fullStr | Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection |
| title_full_unstemmed | Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection |
| title_short | Pyrroloquinoline quinone drives ATP synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection |
| title_sort | pyrroloquinoline quinone drives atp synthesis in vitro and in vivo and provides retinal ganglion cell neuroprotection |
| topic | Pyrroloquinoline quinone (PQQ) Mitochondria Metabolism Metabolomics ATP Retinal ganglion cell |
| url | https://doi.org/10.1186/s40478-023-01642-6 |
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