دورية أكاديمية

A vesicular Warburg effect: Aerobic glycolysis occurs on axonal vesicles for local NAD+ recycling and transport.

التفاصيل البيبلوغرافية
العنوان: A vesicular Warburg effect: Aerobic glycolysis occurs on axonal vesicles for local NAD+ recycling and transport.
المؤلفون: Mc Cluskey M; Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, GIN, Grenoble, France., Dubouchaud H; Univ. Grenoble Alpes, Inserm, U1055, Laboratory of Fundamental and Applied Bioenergetics, LBFA, Grenoble, France., Nicot AS; Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, GIN, Grenoble, France., Saudou F; Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neuroscience, GIN, Grenoble, France.
المصدر: Traffic (Copenhagen, Denmark) [Traffic] 2024 Jan; Vol. 25 (1), pp. e12926. Date of Electronic Publication: 2023 Dec 12.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Wiley Country of Publication: England NLM ID: 100939340 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0854 (Electronic) Linking ISSN: 13989219 NLM ISO Abbreviation: Traffic Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Wiley
Original Publication: Copenhagen, Denmark ; Malden, MA : Munksgaard, c2000-
مواضيع طبية MeSH: NAD*/metabolism , Glycolysis*/physiology, Axons/metabolism ; Adenosine Triphosphate/metabolism ; Pyruvates/metabolism
مستخلص: In neurons, fast axonal transport (FAT) of vesicles occurs over long distances and requires constant and local energy supply for molecular motors in the form of adenosine triphosphate (ATP). FAT is independent of mitochondrial metabolism. Indeed, the glycolytic machinery is present on vesicles and locally produces ATP, as well as nicotinamide adenine dinucleotide bonded with hydrogen (NADH) and pyruvate, using glucose as a substrate. It remains unclear whether pyruvate is transferred to mitochondria from the vesicles as well as how NADH is recycled into NAD+ on vesicles for continuous glycolysis activity. The optimization of a glycolytic activity test for subcellular compartments allowed the evaluation of the kinetics of vesicular glycolysis in the brain. This revealed that glycolysis is more efficient on vesicles than in the cytosol. We also found that lactate dehydrogenase (LDH) enzymatic activity is required for effective vesicular ATP production. Indeed, inhibition of LDH or the forced degradation of pyruvate inhibited ATP production from axonal vesicles. We found LDHA rather than the B isoform to be enriched on axonal vesicles suggesting a preferential transformation of pyruvate to lactate and a concomitant recycling of NADH into NAD + on vesicles. Finally, we found that LDHA inhibition dramatically reduces the FAT of both dense-core vesicles and synaptic vesicle precursors in a reconstituted cortico-striatal circuit on-a-chip. Together, this shows that aerobic glycolysis is required to supply energy for vesicular transport in neurons, similar to the Warburg effect.
(© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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معلومات مُعتمدة: International ERC_ European Research Council
فهرسة مساهمة: Keywords: Warburg effect; aerobic glycolysis; axonal transport; brain-derived neurotrophic factor; cortico-striatal network; dense-core vesicles; lactate dehydrogenase; metabolism; microfluidic device; nicotinamide adenine dinucleotide; synaptic vesicle precursors
المشرفين على المادة: 0U46U6E8UK (NAD)
8L70Q75FXE (Adenosine Triphosphate)
0 (Pyruvates)
تواريخ الأحداث: Date Created: 20231212 Date Completed: 20240129 Latest Revision: 20240227
رمز التحديث: 20240227
DOI: 10.1111/tra.12926
PMID: 38084815
قاعدة البيانات: MEDLINE
الوصف
تدمد:1600-0854
DOI:10.1111/tra.12926