The critical function of NME3 in mitochondrial dynamics and adaptation to glucose starvation revealed by a neonatal defect carrying homozygous mutation

Explore related products in the following collection:

Poster Abstracts - Z118

The critical function of NME3 in mitochondrial dynamics and adaptation to glucose starvation revealed by a neonatal defect carrying homozygous mutation

Zee-Fen Chang^1*, Chih-Wei Chen¹, Hong-Ling Wang¹, Ching-Wen Huang², Tsang Sung Hsieh², Jung-Chi Liao³, Orly Elpeleg⁴, and Hanna Mande⁵
¹Institute of Molecular Medicine, College of Medicine, ²Department of Medicine, College of Medicine, National Taiwan University;³Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei, Taiwan; ⁴Department of Genetic and Metabolic Diseases, Hadassah Hebrew University Medical Center, Jerusalem,⁵Biochemical Genetics, Technion Faculty of Medicine, Haifa, Israel

We report an infant with homozygous mutation in the initiation codon of NME3 gene, which encodes one of NDP kinase isoforms. This infant was born with neurological defects and deceased at 3 months. Our mechanistic investigation demonstrated that NME3 interacts with mitofusins, Mfn1/Mfn2, and promotes the dimerization of mitofusins. NME3 knockdown in normal fibroblasts reduced mitochondrial fusion activity. Consistently, the patient fibroblasts exhibited deficiency in mitochondrial dynamics, aberrant cristae and higher mitochondrial oxidative stress, all of which were reversed by NME3 expression. After glucose deprivation, patient fibroblasts had a significant increase in fragmented mitochondria and cell death due to mitochondrial oxidative stress. Expression of wild-type or catalytic-dead NME3 restored mitochondrial elongation, but only wild-type NME3 reduced glucose starvation-induced oxidative stress and sustained cell viability. Thus, NME3 is critical for mitochondrial fusion independent of the catalytic activity, but in glucose deprivation its catalytic function becomes essential for survival. This investigation suggests the importance of NME3 in mitochondrial dynamics and adaptation to metabolic stress, which deficiencies might contribute to neurological defect developed in the patient.

· · ·

Related Products

Novel Functions of Rab24 in Regulating Blood Glucose Homeostasis and Mitochondrial Activity in the Liver

NOVEL FUNCTIONS OF RAB24 IN REGULATING BLOOD GLUCOSE HOMEOSTASIS AND MITOCHONDRIAL ACTIVITY IN THE LIVER

Growth differentiation factor 15 protects against chronic alcohol- and carbon tetrachloride-induced liver injury

GROWTH DIFFERENTIATION FACTOR 15 PROTECTS AGAINST CHRONIC ALCOHOL- AND CARBON TETRACHLORIDE-INDUCED LIVER INJURY

Vms1 is a release factor for the Ribosome Quality control Complex

VMS1 IS A RELEASE FACTOR FOR THE RIBOSOME QUALITY CONTROL COMPLEX

Identification of mitochondrial RNA granules assembly factors and regulators using an image-based siRNA screen

IDENTIFICATION OF MITOCHONDRIAL RNA GRANULES ASSEMBLY FACTORS AND REGULATORS USING AN IMAGE-BASED SIRNA SCREEN