Publikation:

TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis

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2024

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Buckley, Niall A.
Craxton, Andrew
Sun, Xiao-Ming
Panatta, Emanuele
Pinon, Lucia Giraldez
Beier, Sina
Kalmar, Lajos
Martins, L. Miguel
MacFarlane, Marion
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Cell Death & Disease. Springer. 2024, 15(11), 807. eISSN 2041-4889. Verfügbar unter: doi: 10.1038/s41419-024-07130-6

Zusammenfassung

Dysregulated mitochondrial fusion and fission has been implicated in the pathogenesis of numerous diseases. We have identified a novel function of the p53 family protein TAp73 in regulating mitochondrial dynamics. TAp73 regulates the expression of Optic Atrophy 1 (OPA1), a protein responsible for controlling mitochondrial fusion, cristae biogenesis and electron transport chain function. Disruption of this axis results in a fragmented mitochondrial network and an impaired capacity for energy production via oxidative phosphorylation. Owing to the role of OPA1 in modulating cytochrome c release, TAp73−/− cells display an increased sensitivity to apoptotic cell death, e.g., via BH3-mimetics. We additionally show that the TAp73/OPA1 axis has functional relevance in the upper airway, where TAp73 expression is essential for multiciliated cell differentiation and function. Consistently, ciliated epithelial cells of Trp73 −/− (global p73 knock-out) mice display decreased expression of OPA1 and perturbations of the mitochondrial network, which may drive multiciliated cell loss. In support of this, Trp73 and OPA1 gene expression is decreased in chronic obstructive pulmonary disease (COPD) patients, a disease characterised by alterations in mitochondrial dynamics. We therefore highlight a potential mechanism involving the loss of p73 in COPD pathogenesis. Our findings also add to the growing body of evidence for growth-promoting roles of TAp73 isoforms.

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570 Biowissenschaften, Biologie

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ISO 690BUCKLEY, Niall A., Andrew CRAXTON, Xiao-Ming SUN, Emanuele PANATTA, Lucia Giraldez PINON, Sina BEIER, Lajos KALMAR, Ivano AMELIO, L. Miguel MARTINS, Marion MACFARLANE, 2024. TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis. In: Cell Death & Disease. Springer. 2024, 15(11), 807. eISSN 2041-4889. Verfügbar unter: doi: 10.1038/s41419-024-07130-6
BibTex
@article{Buckley2024-11-08TAp73-71856,
  title={TAp73 regulates mitochondrial dynamics and multiciliated cell homeostasis through an OPA1 axis},
  year={2024},
  doi={10.1038/s41419-024-07130-6},
  number={11},
  volume={15},
  journal={Cell Death & Disease},
  author={Buckley, Niall A. and Craxton, Andrew and Sun, Xiao-Ming and Panatta, Emanuele and Pinon, Lucia Giraldez and Beier, Sina and Kalmar, Lajos and Amelio, Ivano and Martins, L. Miguel and MacFarlane, Marion},
  note={Article Number: 807}
}
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