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PINK1 regulates the balance between mitochondrial homeostasis and bioenergy supply and demand via the PINK1\/Parkin pathway, Na+\/Ca2+ exchange, and other pathways. (2) Methods: In this study, we synthesized positively charged carbon dots (CA-PEI CDs) using citric acid (CA) and polyethyleneimine (PEI) and used them as vectors to express PINK1 genes in the APP\/PS1-N2a cell line to determine mitochondrial function, electron transport chain (ETC) activity, and ATP-related metabolomics. (3) Results: Our findings showed that the CA-PEI CDs exhibit the characteristics of photoluminescence, low toxicity, and concentrated DNA. They are ideal biological carriers for gene delivery. PINK1 overexpression significantly increased the mitochondrial membrane potential in APP\/PS1-N2a cells and reduced reactive-oxygen-species generation and A\u03b21-40 and A\u03b21-42 levels. An increase in the activity of NADH ubiquinone oxidoreductase (complex I, CI) and cytochrome C oxidase (complex IV, CIV) induces the oxidative phosphorylation of mitochondria, increasing ATP generation. (4) Conclusions: These findings indicate that the PINK gene can alleviate AD by increasing bioenergetic metabolism, reducing A\u03b21-40 and A\u03b21-42, and increasing ATP production.<\/jats:p>","DOI":"10.3390\/molecules29091907","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T08:08:27Z","timestamp":1713859707000},"page":"1907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Electropositive Citric Acid-Polyethyleneimine Carbon Dots Carrying the PINK1 Gene Regulate ATP-Related Metabolic Dysfunction in APP\/PS1-N2a Cells"],"prefix":"10.3390","volume":"29","author":[{"given":"Si","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment of Hainan Province, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment of Hainan Province, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhen","family":"Luo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment of Hainan Province, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Brain Science and Health Translational Medicine Research Center in Tropical Environment of Hainan Province, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Medical College, Gannan Medical University, Ganzhou 341000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7126-1781","authenticated-orcid":false,"given":"Haiying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hainan Provincial Key Laboratory of Carcinogenesis and Intervention, Hainan Medical University, Haikou 571199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1007\/s12264-018-0249-z","article-title":"Clinical research on Alzheimer\u2019s disease: Progress and perspectives","volume":"34","author":"Sun","year":"2018","journal-title":"Neurosci. 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