2026-07-22T00:33:50Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/258492025-12-18T12:55:45Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587
Repisalud
author
Hernansanz-Agustín, Pablo
author
Morales-Vidal, Carmen
author
Calvo, Enrique
author
Natale, Paolo
author
Martí-Mateos, Yolanda
author
Jaroszewicz, Sara Natalia
author
Cabrera-Alarcón, José Luis
author
Acín-Pérez, Rebeca
author
López-Montero, Iván
author
Vázquez, Jesús
author
Enríquez, José Antonio
funder
Ministerio de Ciencia e Innovación (España)
funder
International Human Frontier Science Program Organization
funder
Fondation Leducq
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia, Innovación y Universidades (España)
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
funder
Comunidad de Madrid (España)
2024-12-04T10:08:58Z
2024-12-04T10:08:58Z
2024-11-14
Cell. 2024 Nov 14;187(23):6599-6613.e21.
Cell
39303716
https://hdl.handle.net/20.500.12105/25849
Eukaryotic cell function and survival rely on the use of a mitochondrial H electrochemical gradient (Δp), which is composed of an inner mitochondrial membrane (IMM) potential (ΔΨmt) and a pH gradient (ΔpH). So far, ΔΨmt has been assumed to be composed exclusively of H. Here, using a rainbow of mitochondrial and nuclear genetic models, we have discovered that a Na gradient equates with the H gradient and controls half of ΔΨmt in coupled-respiring mammalian mitochondria. This parallelism is controlled by the activity of the long-sought Na-specific Na/H exchanger (mNHE), which we have identified as the P-module of complex I (CI). Deregulation of this mNHE function, without affecting the canonical enzymatic activity or the assembly of CI, occurs in Leber's hereditary optic neuropathy (LHON), which has profound consequences in ΔΨmt and mitochondrial Ca homeostasis and explains the previously unknown molecular pathogenesis of this neurodegenerative disease.
eng
LHON
Na(+) gradient
complex I
mitochondrial Na(+)/H(+) antiporter
ΔΨmt
A transmitochondrial sodium gradient controls membrane potential in mammalian mitochondria.
research article
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URL
https://repisalud.isciii.es/bitstreams/9aa885de-53a7-4f4e-b6be-291e97748e8f/download
File
MD5
9f19cd2cf26b72fdfc7feb2f443d324c
11518949
application/pdf
A transmitochondrial sodium gradient_Cell_2024.pdf