Work

Oxidative stress imbalance and cellular damage mediated by the ND4 G11778A mutation

Year: 2026

Type: article

Abstract: The mechanisms underlying cellular damage induced by the mitochondrially encoded NADH dehydrogenase subunit 4 (MT-ND4) with R340H mutation caused by the variant m.11778G > A in complex I are intricate. Numerous studies indicate that mitochondria play a primary role in cellular death due to this mutation. However, the detailed pathological effects remain incompletely elucidated. To decipher the specific impacts of this mutation on cellular death, mitochondrial dysfunction was investigated in 661 W cells expressing exogenous Mut-ND4 (m.G11778A). Importantly, the oxygen consumption rate (OCR) assessed by Seahorse XF analyzer exhibited a significant decrease under galactose conditions and an excessive production of reactive oxygen species (ROS). Conversely, the activity levels of catalase (CAT), superoxide dismutase (SOD), and total glutathione (T-GSH) were decreased, leading to increased cell death in cells expressing Mut-ND4 (m.G11778A) under galactose conditions. In addition, structural disruptions in the optic nerves of mice subjected to Mut-ND4-AAV infection were revealed. These findings suggest that Mut-ND4 (m.G11778A) contributes to cellular injury and an oxidative stress imbalance, characterized by decreased mitochondrial oxygen consumption, increased oxidative products, and reduced antioxidant capacity.

Source: Scientific Reports

DOI: 10.1038/s41598-026-40061-0