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Analysis of institutional authors

Mesa-Ciller CAuthorGuajardo-Grence AAuthorEgea JAuthorAragones JAuthorUrrutia AaCorresponding Author

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August 8, 2022
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Article

Unique expression of the atypical mitochondrial subunit NDUFA4L2 in cerebral pericytes fine tunes HIF activity in response to hypoxia

Publicated to: Journal Of Cerebral Blood Flow And Metabolism. 43 (1): 271678X221118236-58 - 2023-01-01 43(1), DOI: 10.1177/0271678X221118236

Authors:

Mesa-Ciller, C; Turiel, G; Guajardo-Grence, A; Lopez-Rodriguez, AB; Egea, J; De Bock, K; Aragonés, J; Urrutia, AA
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Affiliations

Carlos III Hlth Inst, CIBER Enfermedades Cardiovasc, Madrid, Spain - Author
CIBER de Enfermedades Cardiovasculares, Carlos III Health Institute, Madrid, Spain. - Author
Hosp Univ Santa Cristina, Inst Invest Sanitaria Hosp Univ Princesa, Mol Neuroinflammat & Neuronal Plast Res Lab, Madrid, Spain - Author
Instituto Teófilo Hernando, Departamento de Farmacología y Terapéutica, Facultad de Medicina, UAM, Madrid, Spain. - Author
Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETH Zürich), Zürich, Switzerland. - Author
Molecular Neuroinflammation and Neuronal Plasticity Research Laboratory, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain. - Author
Swiss Fed Inst Technol, Dept Hlth Sci & Technol, Lab Exercise & Hlth, Zurich, Switzerland - Author
UAM, Inst Teofilo Hernando, Dept Farmacol & Terapeut, Fac Med, Madrid, Spain - Author
Unidad de Investigación, Hospital de Santa Cristina, Instituto de Investigación del Hospital Universitario La Princesa, Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. - Author
Univ Autonoma Madrid, Inst Invest Hosp Univ La Princesa, Hosp Santa Cristina, Dept Med,Unidad Invest, Madrid, Spain - Author
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Abstract

A central response to insufficient cerebral oxygen delivery is a profound reprograming of metabolism, which is mainly regulated by the Hypoxia Inducible Factor (HIF). Among other responses, HIF induces the expression of the atypical mitochondrial subunit NDUFA4L2. Surprisingly, NDUFA4L2 is constitutively expressed in the brain in non-hypoxic conditions. Analysis of publicly available single cell transcriptomic (scRNA-seq) data sets coupled with high-resolution multiplexed fluorescence RNA in situ hybridization (RNA F.I.S.H.) revealed that in the murine and human brain NDUFA4L2 is exclusively expressed in mural cells with the highest levels found in pericytes and declining along the arteriole-arterial smooth muscle cell axis. This pattern was mirrored by COX4I2, another atypical mitochondrial subunit. High NDUFA4L2 expression was also observed in human brain pericytes in vitro, decreasing when pericytes are muscularized and further induced by HIF stabilization in a PHD2/PHD3 dependent manner. In vivo, Vhl conditional inactivation in pericyte targeting Ng2-cre transgenic mice dramatically induced NDUFA4L2 expression. Finally NDUFA4L2 inactivation in pericytes increased oxygen consumption and therefore the degree of HIF pathway induction in hypoxia. In conclusion our work reveals that NDUFA4L2 together with COX4I2 is a key hypoxic-induced metabolic marker constitutively expressed in pericytes coupling mitochondrial oxygen consumption and cellular hypoxia response.
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Keywords

alphabraincomplexfamilyhealthhifhif-1-alphametabolismoxygenpericytephysiologyBrainHifNdufa4l2OxygenPericyte

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Cerebral Blood Flow And Metabolism due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 32/186, thus managing to position itself as a Q1 (Primer Cuartil), in the category Endocrinology & Metabolism.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.47. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.15 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-05, the following number of citations:

  • WoS: 7
  • Scopus: 6
  • Europe PMC: 2
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-05:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 19.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 19 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 10.
  • The number of mentions on the social network X (formerly Twitter): 13 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/10486/709080
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Switzerland.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (MESA CILLER, CLAUDIA JULIA) and Last Author (URRUTIA ELORDUY, ANDRES AMALIO).

the author responsible for correspondence tasks has been URRUTIA ELORDUY, ANDRES AMALIO.

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Awards linked to the item

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by grant SI1/PJI/201900399 from Universidad Autonoma de Madrid and Comunidad Autonoma de Madrid. CMC is supported by the FPI fellowship from Ministerio de Ciencia e Innovacion. GT is funded through an ERC Starting grant by KDB (716140). KDB is endowed by the Schulthess foundation. AGG is supported by the FPI UAM fellowship from Universidad Autonoma de Madrid. AU is supported by the Comunidad de Madrid "Atraccion de Talento Program".
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