ReviewIUBMB life2020
The malate-aspartate shuttle (Borst cycle): How it started and developed into a major metabolic pathway.
Review in IUBMB life, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 158 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
158 citing papers in PubMed, 1 synthesis or guideline pooled it, 226 citations in OpenAlex.
- Effect of Concomitant Use of Analgesics on Prognosis in Patients Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.Frontiers in immunology · 2022Pooled it
- Machine learning and data-driven inverse modeling of metabolomics unveil key processes of active aging.NPJ systems biology and applications · 2025Trial
- Coordinated regulation of the metaboproteome by Hsp90 chaperones controls metabolic plasticity.iScience · 2026Article
- Mito-nuclear incompatibility disrupts acyl-CoA oxidase 1/acyl-CoA oxidase 3-mediated mitochondria-peroxisome metabolic coordination in black soldier flies.Molecular biology and evolution · 2026Article
- Remodeling of mitochondrial dynamics by metabolic pathways couples to oncogenic growth inScience advances · 2026Article
- Carvacrol Modulates Cadmium-Induced Behavioral, Biochemical, Histopathological, and Metabolomic Alterations in rats.Biological trace element research · 2026Article
- N-Acetylaspartate Synthesis as a Thermodynamic Relief Mechanism for Mitochondrial Aspartate Aminotransferase.bioRxiv : the preprint server for biology · 2026Article
- The diversity of terminal electron acceptors across eukaryotes.Trends in biochemical sciences · 2026Review
- Redox coupling of lactate and β-hydroxybutyrate: An inter-organ circuit linking metabolic flexibility, mitochondrial adaptation, and disease.Redox biology · 2026Review
- Loss of the mitochondrial SAM transporter reveals a lipoylation-dependent metabolic vulnerability in the postnatal heart.Science advances · 2026Article
- Oxaloacetate inhibition of succinate dehydrogenase: mechanism and physiological implications.American journal of physiology. Cell physiology · 2026Review
- Oxaloacetate damages mitochondria by perturbing MIC60-dependent membrane remodeling.PLoS biology · 2026Article
- The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes.The FEBS journal · 2026Article
- Mitochondrial control of amino acid catabolism by a fasting-inducible mitochondrial carrier.Science advances · 2026Article
- Metformin's disruption of gluconeogenesis in type 2 diabetes impairments of the cori and alanine cycles as hidden drivers of metabolic waste accumulation, NF-κBHIF-1α-mediated low-grade inflammation, and multisystem dysfunction.Problemy endokrinologii · 2026Review
- Regulation and clinical manifestations of gluconeogenesis dysfunction.npj metabolic health and disease · 2026Review
- Dynamic assembly of malate dehydrogenase-citrate synthase multienzyme complex in the mitochondria.eLife · 2026Article
- Adaptive plasticity of aspartate metabolism in succinate dehydrogenase-deficient cancer cells.bioRxiv : the preprint server for biology · 2026Article
- Metabolic Mechanisms of Neutrophil Phagocytic Activity in Patients with Widespread Purulent Peritonitis Bacterial Peritonitis Before and After Surgery.International journal of molecular sciences · 2026Article
- Oncolytic virus hijacks GOT1 and pyrimidinosomes to fuel pyrimidine synthesis for replication in tumor cells.Tumour virus research · 2026Article
98 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
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This article presents a personal and critical review of the history of the malate-aspartate shuttle (MAS), starting in 1962 and ending in 2020. The MAS was initially proposed as a route for the oxidation of cytosolic NADH by the mitochondria in Ehrlich ascites cell tumor lacking other routes, and to explain the need for a mitochondrial aspartate aminotransferase (glutamate oxaloacetate transaminase 2 [GOT2]). The MAS was soon adopted in the field as a major pathway for NADH oxidation in mammalian tissues, such as liver and heart, even though the energetics of the MAS remained a mystery. Only in the 1970s, LaNoue and coworkers discovered that the efflux of aspartate from mitochondria, an essential step in the MAS, is dependent on the proton-motive force generated by the respiratory chain: for every aspartate effluxed, mitochondria take up one glutamate and one proton. This makes the MAS in practice uni-directional toward oxidation of cytosolic NADH, and explains why the free NADH/NAD ratio is much higher in the mitochondria than in the cytosol. The MAS is still a very active field of research. Most recently, the focus has been on the role of the MAS in tumors, on cells with defects in mitochondria and on inborn errors in the MAS. The year 2019 saw the discovery of two new inborn errors in the MAS, deficiencies in malate dehydrogenase 1 and in aspartate transaminase 2 (GOT2). This illustrates the vitality of ongoing MAS research.
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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.