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Mitochondrial energy metabolism and p70 ribosomal protein S6 kinase (p70S6K) play significant roles in AD pathology. However, the potential relationship between them is unclear. In this study, bioinformatics methods were initially applied to analyze the transcriptomic data in the CA1 and the primary visual cortex of patients with AD and A\u03b242-treated SH-SY5Y cells. By applying secreted A\u03b242 and p70S6K gene silencing in cells, we explored disorders in mitochondrial function and the regulatory roles of p70S6K by flow cytometry, laser scanning confocal microscopy, high-performance liquid chromatography, Western blotting, and quantitative reverse transcription PCR. The study reveals that impaired mitochondrial energy metabolism is a potential pathological feature of AD and that p70S6K gene silencing reversed most of the changes induced by A\u03b242, such as the activities of the electron transport chain complexes I and III, as well as ATP synthase, ATP production, generation of reactive oxygen species, mitochondrial membrane potential, and phosphorylation of AMPK, PINK1, and Parkin, all of which are required for mitochondria to function properly in the cell.<\/jats:p>","DOI":"10.3390\/metabo14070369","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T09:06:07Z","timestamp":1719824767000},"page":"369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Impaired Mitochondrial Energy Metabolism Regulated by p70S6K: A Putative Pathological Feature in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Wenyu","family":"Gu","sequence":"first","affiliation":[{"name":"Key Laboratory of Tropical Bioresources of the Educational Ministry of China, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"},{"name":"Laboratory of Biopharmaceuticals and Molecular Pharmacology, One Health Cooperative Innovation Center, Hainan University, Haikou 570228, China"},{"name":"Department of Biotechnology, School of Life and Health Sciences, Hainan University, Haikou 570228, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinli","family":"Cong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Bioresources of the Educational Ministry of China, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"},{"name":"Laboratory of Biopharmaceuticals and Molecular Pharmacology, One Health Cooperative Innovation Center, Hainan University, Haikou 570228, China"},{"name":"Department of Biotechnology, School of Life and Health Sciences, Hainan University, Haikou 570228, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yechun","family":"Pei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Bioresources of the Educational Ministry of China, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"},{"name":"Laboratory of Biopharmaceuticals and Molecular Pharmacology, One Health Cooperative Innovation Center, Hainan University, Haikou 570228, China"},{"name":"Department of Biotechnology, School of Life and Health Sciences, Hainan University, Haikou 570228, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuela Manka\u2019a","family":"Che Ajuyo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Bioresources of the Educational Ministry of China, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"},{"name":"Laboratory of Biopharmaceuticals and Molecular Pharmacology, One Health Cooperative Innovation Center, Hainan University, Haikou 570228, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Min","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Bioresources of the Educational Ministry of China, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"},{"name":"Laboratory of Biopharmaceuticals and Molecular Pharmacology, One Health Cooperative Innovation Center, Hainan University, Haikou 570228, China"},{"name":"Department of Biotechnology, School of Life and Health Sciences, Hainan University, Haikou 570228, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2086-1663","authenticated-orcid":false,"given":"Dayong","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Tropical Bioresources of the Educational Ministry of China, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China"},{"name":"Laboratory of Biopharmaceuticals and Molecular Pharmacology, One Health Cooperative Innovation Center, Hainan University, Haikou 570228, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ma, C., Hong, F., and Yang, S. 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