NDUFB7 mutations cause brain neuronal defects, lactic acidosis, and mitochondrial dysfunction in humans and zebrafish
Journal
Cell Death Discovery
Journal Volume
11
Journal Issue
1
ISSN
2058-7716
Date Issued
2025-03-01
Author(s)
Yen-Lin Chen
Brian Hon-Yin Chung
Masakazu Mimaki
Shumpei Uchino
Christopher Chun-Yun Mak
Wei-Chen Wang
Yu-Li Lin
Abstract
Complex I of the mitochondrial electron transfer chain is one of the largest membrane protein assemblies ever discovered. A patient carrying a homozygous NDUFB7 intronic mutation died within two months after birth due to cardiorespiratory defects, preventing further study. Here, we report another patient with compound heterozygous mutations in NDUFB7 who suffers from pons abnormality, lactic acidosis, prematurity, prenatal and postnatal growth deficiency, incomplete closure of the abdominal wall (ventral hernia), and a poorly functioning gastrointestinal tract (pseudo-obstruction). We demonstrated that the patient’s skin fibroblasts are deficient in Complex I assembly and reduced supercomplex formation. This report further broadens the spectrum of mitochondrial disorders. The patient has had several surgeries. After receiving treatment with Coenzyme Q10 and vitamin B complex, she has remained stable up to this point. To further explore the functionality of NDUFB7 in vivo, we knocked down Ndufb7 in zebrafish embryos. This resulted in brain ventricle and neuronal defects, elevated lactic acid levels, and reduced oxygen consumption, indicating defective mitochondrial respiration. These phenotypes can be specifically rescued by ectopic expression of ndufb7. More importantly, Mitoquinone mesylate (MitoQ), a common remedy for mitochondrial disorders, can ameliorate these conditions. These results suggest a role for NDUFB7 in mitochondrial activity and the suitability of the zebrafish model for further drug screening and the development of therapeutic strategies for this rare disease.
SDGs
Publisher
Springer Science and Business Media LLC
Description
Article number 82
Type
journal article