NDUFS4, a mitochondrial complex I subunit, is essential for T-cell metabolic fitness and immune function.

ABSTRACT:

Introduction

Mitochondrial metabolism is essential for T-cell function, but the roles of individual electron transport chain (ETC) components are unclear. Here, we aimed to explore the role of mitochondrial complex I (CI) subunit NADH:ubiquinone oxidoreductase iron-sulfur protein 4 (NDUFS4) in T-cell metabolic fitness and immunity.

Methods

We used a T cell-specific Ndufs4 knockout mouse model to find that NDUFS4 deficiency disrupts CI function, leading to metabolic and redox imbalances. Additionally, T cells from a patient with Leigh syndrome induced by NDUFS4 loss-of-function were analyzed.

Results

Ndufs4-deficient T cells exhibit impaired OXPHOS, reduced respiratory capacity, and increased glycolysis, accompanied by reactive oxygen species (ROS) accumulation and def

SUBMITTER: Shamriz O 

PROVIDER: S-EPMC12819820 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature