Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function. / Sanz-Morello, Berta; Pfisterer, Ulrich; Winther Hansen, Nikolaj; Demharter, Samuel; Thakur, Ashish; Fujii, Katsunori; Levitskii, Sergey A; Montalant, Alexia; Korshunova, Irina; Mammen, Pradeep Pa; Kamenski, Piotr; Noguchi, Satoru; Aldana, Blanca Irene; Hougaard, Karin Sørig; Perrier, Jean-François; Khodosevich, Konstantin.

In: The EMBO Journal, Vol. 39, No. 18, e105759, 2020, p. 1-21.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Sanz-Morello, B, Pfisterer, U, Winther Hansen, N, Demharter, S, Thakur, A, Fujii, K, Levitskii, SA, Montalant, A, Korshunova, I, Mammen, PP, Kamenski, P, Noguchi, S, Aldana, BI, Hougaard, KS, Perrier, J-F & Khodosevich, K 2020, 'Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function', The EMBO Journal, vol. 39, no. 18, e105759, pp. 1-21. https://doi.org/10.15252/embj.2020105759

APA

Sanz-Morello, B., Pfisterer, U., Winther Hansen, N., Demharter, S., Thakur, A., Fujii, K., Levitskii, S. A., Montalant, A., Korshunova, I., Mammen, P. P., Kamenski, P., Noguchi, S., Aldana, B. I., Hougaard, K. S., Perrier, J-F., & Khodosevich, K. (2020). Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function. The EMBO Journal, 39(18), 1-21. [e105759]. https://doi.org/10.15252/embj.2020105759

Vancouver

Sanz-Morello B, Pfisterer U, Winther Hansen N, Demharter S, Thakur A, Fujii K et al. Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function. The EMBO Journal. 2020;39(18):1-21. e105759. https://doi.org/10.15252/embj.2020105759

Author

Sanz-Morello, Berta ; Pfisterer, Ulrich ; Winther Hansen, Nikolaj ; Demharter, Samuel ; Thakur, Ashish ; Fujii, Katsunori ; Levitskii, Sergey A ; Montalant, Alexia ; Korshunova, Irina ; Mammen, Pradeep Pa ; Kamenski, Piotr ; Noguchi, Satoru ; Aldana, Blanca Irene ; Hougaard, Karin Sørig ; Perrier, Jean-François ; Khodosevich, Konstantin. / Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function. In: The EMBO Journal. 2020 ; Vol. 39, No. 18. pp. 1-21.

Bibtex

@article{5765d64220934e1cbcde9e188ec918d1,
title = "Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function",
abstract = "Parvalbumin-positive (PV+ ) fast-spiking interneurons are essential to control the firing activity of principal neuron ensembles, thereby regulating cognitive processes. The high firing frequency activity of PV+ interneurons imposes high-energy demands on their metabolism that must be supplied by distinctive machinery for energy generation. Exploring single-cell transcriptomic data for the mouse cortex, we identified a metabolism-associated gene with highly restricted expression to PV+ interneurons: Cox6a2, which codes for an isoform of a cytochrome c oxidase subunit. Cox6a2 deletion in mice disrupts perineuronal nets and enhances oxidative stress in PV+ interneurons, which in turn impairs the maturation of their morphological and functional properties. Such dramatic effects were likely due to an essential role of COX6A2 in energy balance of PV+ interneurons, underscored by a decrease in the ATP-to-ADP ratio in Cox6a2-/- PV+ interneurons. Energy disbalance and aberrant maturation likely hinder the integration of PV+ interneurons into cortical neuronal circuits, leading to behavioral alterations in mice. Additionally, in a human patient bearing mutations in COX6A2, we found a potential association of the mutations with mental/neurological abnormalities.",
author = "Berta Sanz-Morello and Ulrich Pfisterer and {Winther Hansen}, Nikolaj and Samuel Demharter and Ashish Thakur and Katsunori Fujii and Levitskii, {Sergey A} and Alexia Montalant and Irina Korshunova and Mammen, {Pradeep Pa} and Piotr Kamenski and Satoru Noguchi and Aldana, {Blanca Irene} and Hougaard, {Karin S{\o}rig} and Jean-Fran{\c c}ois Perrier and Konstantin Khodosevich",
year = "2020",
doi = "10.15252/embj.2020105759",
language = "English",
volume = "39",
pages = "1--21",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "18",

}

RIS

TY - JOUR

T1 - Complex IV subunit isoform COX6A2 protects fast-spiking interneurons from oxidative stress and supports their function

AU - Sanz-Morello, Berta

AU - Pfisterer, Ulrich

AU - Winther Hansen, Nikolaj

AU - Demharter, Samuel

AU - Thakur, Ashish

AU - Fujii, Katsunori

AU - Levitskii, Sergey A

AU - Montalant, Alexia

AU - Korshunova, Irina

AU - Mammen, Pradeep Pa

AU - Kamenski, Piotr

AU - Noguchi, Satoru

AU - Aldana, Blanca Irene

AU - Hougaard, Karin Sørig

AU - Perrier, Jean-François

AU - Khodosevich, Konstantin

PY - 2020

Y1 - 2020

N2 - Parvalbumin-positive (PV+ ) fast-spiking interneurons are essential to control the firing activity of principal neuron ensembles, thereby regulating cognitive processes. The high firing frequency activity of PV+ interneurons imposes high-energy demands on their metabolism that must be supplied by distinctive machinery for energy generation. Exploring single-cell transcriptomic data for the mouse cortex, we identified a metabolism-associated gene with highly restricted expression to PV+ interneurons: Cox6a2, which codes for an isoform of a cytochrome c oxidase subunit. Cox6a2 deletion in mice disrupts perineuronal nets and enhances oxidative stress in PV+ interneurons, which in turn impairs the maturation of their morphological and functional properties. Such dramatic effects were likely due to an essential role of COX6A2 in energy balance of PV+ interneurons, underscored by a decrease in the ATP-to-ADP ratio in Cox6a2-/- PV+ interneurons. Energy disbalance and aberrant maturation likely hinder the integration of PV+ interneurons into cortical neuronal circuits, leading to behavioral alterations in mice. Additionally, in a human patient bearing mutations in COX6A2, we found a potential association of the mutations with mental/neurological abnormalities.

AB - Parvalbumin-positive (PV+ ) fast-spiking interneurons are essential to control the firing activity of principal neuron ensembles, thereby regulating cognitive processes. The high firing frequency activity of PV+ interneurons imposes high-energy demands on their metabolism that must be supplied by distinctive machinery for energy generation. Exploring single-cell transcriptomic data for the mouse cortex, we identified a metabolism-associated gene with highly restricted expression to PV+ interneurons: Cox6a2, which codes for an isoform of a cytochrome c oxidase subunit. Cox6a2 deletion in mice disrupts perineuronal nets and enhances oxidative stress in PV+ interneurons, which in turn impairs the maturation of their morphological and functional properties. Such dramatic effects were likely due to an essential role of COX6A2 in energy balance of PV+ interneurons, underscored by a decrease in the ATP-to-ADP ratio in Cox6a2-/- PV+ interneurons. Energy disbalance and aberrant maturation likely hinder the integration of PV+ interneurons into cortical neuronal circuits, leading to behavioral alterations in mice. Additionally, in a human patient bearing mutations in COX6A2, we found a potential association of the mutations with mental/neurological abnormalities.

U2 - 10.15252/embj.2020105759

DO - 10.15252/embj.2020105759

M3 - Journal article

C2 - 32744742

VL - 39

SP - 1

EP - 21

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 18

M1 - e105759

ER -

ID: 246635086