2026-07-22T00:33:36Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/258492025-12-18T12:55:45Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc 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 author 2024-11-14 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. Cell. 2024 Nov 14;187(23):6599-6613.e21. Cell 39303716 https://hdl.handle.net/20.500.12105/25849 LHON Na(+) gradient complex I mitochondrial Na(+)/H(+) antiporter ΔΨmt A transmitochondrial sodium gradient controls membrane potential in mammalian mitochondria.