ArticleCell metabolism2020
NAD+ Regeneration Rescues Lifespan, but Not Ataxia, in a Mouse Model of Brain Mitochondrial Complex I Dysfunction.
Article in Cell metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 105 citations in OpenAlex.
- Remodeling of mitochondrial dynamics by metabolic pathways couples to oncogenic growth inScience advances · 2026Article
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- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycaemic control.Nature metabolism · 2026Article
- Methylene blue restores NADJournal of orthopaedic translation · 2026Article
- Adipocyte NADH dehydrogenase reverses circadian and diet-induced metabolic syndrome.Nature metabolism · 2026Article
- DHODH turns cytosolic, yet cells keep growing.Nature metabolism · 2026Article
- Ectopic expression of cytosolic DHODH uncouples de novo pyrimidine biosynthesis from mitochondrial electron transport.Nature metabolism · 2026Article
- A genetic screen for modifiers of cohesin clustering identifies regulators of genome folding.Science advances · 2026Article
- CDCP1/mitochondrial Src axis increases electron transport chain function to promote metastasis in triple-negative breast cancer.British journal of cancer · 2025Article
- NADH dehydrogenase reverses dietary and clock metabolic syndrome.bioRxiv : the preprint server for biology · 2025Article
- Metformin inhibits mitochondrial complex I in intestinal epithelium to promote glycemic control.bioRxiv : the preprint server for biology · 2025Article
- Geometrically-engineered human motor assembloids-on-a-chip for neuromuscular interaction readout and hypoxia-driven disease modeling.Nature communications · 2025Article
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Mitochondrial complex I deficiency induces Alzheimer's disease-like signatures that are reversible by targeted therapy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Impaired mitochondrial metabolism is a critical cancer vulnerability for MYC inhibitors.Science advances · 2025Article
- Dual-Responsive Multi-Functional Silica Nanoparticles With Repaired Mitochondrial Functions for Efficient Alleviation of Spinal Cord Injury.Exploration (Beijing, China) · 2025Article
- Xenotopic synthetic biology: Prospective tools for delaying aging and age-related diseases.Science advances · 2025Review
- AIF3 splicing variant elicits mitochondrial malfunction via the concurrent dysregulation of electron transport chain and glutathione-redox homeostasis.Nature communications · 2025Article
- Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment.Frontiers in cell and developmental biology · 2025Article
- Metformin targets mitochondrial complex I to lower blood glucose levels.Science advances · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial complex I regenerates NAD+ and proton pumps for TCA cycle function and ATP production, respectively. Mitochondrial complex I dysfunction has been implicated in many brain pathologies including Leigh syndrome and Parkinson's disease. We sought to determine whether NAD+ regeneration or proton pumping, i.e., bioenergetics, is the dominant function of mitochondrial complex I in protection from brain pathology. We generated a mouse that conditionally expresses the yeast NADH dehydrogenase (NDI1), a single enzyme that can replace the NAD+ regeneration capability of the 45-subunit mammalian mitochondrial complex I without proton pumping. NDI1 expression was sufficient to dramatically prolong lifespan without significantly improving motor function in a mouse model of Leigh syndrome driven by the loss of NDUFS4, a subunit of mitochondrial complex I. Therefore, mitochondrial complex I activity in the brain supports organismal survival through its NAD+ regeneration capacity, while optimal motor control requires the bioenergetic function of mitochondrial complex I.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.