Beta-Amyloid Suppresses Mitochondrial ATP Production in Human Neuroblastoma Cells

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Yuliya A. Zagryadskaya¹, Semen V. Nesterov², Vladimir A. Mitkevich^3,a*, Sergey A. Kozin³, Anastasia K. Kryuchkova¹, Galina Yu. Lomakina⁴, Mikhail S. Karbyshev^5,6, Eduard V. Bocharov^1,7, Alexander A. Makarov³, and Ivan S. Okhrimenko^1,b*

¹Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia

²National Research Center “Kurchatov Institute”, 123182 Moscow, Russia

³Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia

⁴Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia

⁵Research Division, Moscow Polytechnic University, 107023 Moscow, Russia

⁶Department of Biochemistry and Molecular Biology, Institute of Pharmaceutical and Medicinal Chemistry, Pirogov Russian National Research Medical University, 117513 Moscow, Russia

⁷Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 10, 2025; Revised: December 11, 2025; Accepted: December 12, 2025

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β-Amyloid peptides (Aβ), which play a crucial role in the pathogenesis of Alzheimer’s disease by forming toxic oligomeric species, are known to affect mitochondrial function. In this study, luciferin-luciferase assay was used to assess changes in ATP production by mitochondria isolated from human neuroblastoma SH-SY5Y cells cultured in the presence of monomeric Aβ at a nanomolar concentration. ATP synthesis rates were measured in the presence of substrates specific for respiratory chain complexes I, II, and IV alongside inhibitors targeting the other complexes. Aβ significantly reduced both the rate of ATP generation and amount of ATP synthesized by mitochondria. This effect of Aβ on ATP synthesis did not result from a direct influence on the respiratory chain complexes I, II, and IV. Our findings provide insights into possible causes of mitochondrial dysfunction in neurons in Alzheimer’s disease.

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KEY WORDS: Alzheimer’s disease, molecular mechanisms, Aβ peptide, mitochondria, ATP, ADP, luciferin-luciferase assay, human neuroblastoma SH-SY5Y cells, respiratory chain complexes I, II, and IV, MTT test, electron transport chain, ETC

DOI: 10.1134/S0006297925602060

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