Comparison between healthy and dysfunctional mitochondria, highlighting the key mechanisms of mitochondrial dysfunction. ETC: Electron transport chain; ROS: Reactive oxygen species.

Comparison between healthy and dysfunctional mitochondria, highlighting the key mechanisms of mitochondrial dysfunction. ETC: Electron transport chain; ROS: Reactive oxygen species.

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Mitochondria are widely considered the “power hub” of the cell because of their pivotal roles in energy metabolism and oxidative phosphorylation. However, beyond the production of ATP, which is the major source of chemical energy supply in eukaryotes, mitochondria are also central to calcium homeostasis, reactive oxygen species (ROS) balance, and c...

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... shown in Figure 1, the mitochondria generate small molecule storage of chemical energy known as adenosine triphosphate (ATP) via electron transport-linked phosphorylation, otherwise known as oxidative phosphorylation (OXPHOS). The OXPHOS pathway utilizes five enzyme complexes in the inner membrane of the mitochondria to produce ATP as it progresses through the respiratory chain. ...
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... stress resulting from the dysregulated generation of ROS can lead to impairments in the OXPHOS machinery, causing an imbalance in the mitochondrial redox potential and significant loss of mitochondrial functions (Figure 1). Impairments to mitochondrial function could result in decreased ATP generation, calcium overload, and unbalanced apoptosis [2,6,9]. ...
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... oxidative stress, Nrf2 is now a well-known drug target in many neurodegenerative diseases, most of which are associated with mitochondrial dysfunction [23,175,176]. Hence, the ability of a compound of interest to activate Nrf2-mediated antioxidative response is relevant for assessing its antioxidant capacity as a mitochondrial modulator [114,171] . Compounds 1, 2, 7-9, 14, 16, 18, 21, 23, 24, 27, 29, 32, 37, 42, 46, 53, and 54 activate the Nrf2-mediated antioxidative ...
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... of caspase-3, -6, -7, and -9, which subsequently initiates cell death [115,185]. However, the Bcl-2 family includes several anti-apoptotic members such as Bcl-2, Bcl-xL, Mcl-1, and Bcl-w. For the maintenance of proper cellular function, it is important to establish a steady balance between pro-apoptotic and anti-apoptotic markers [115,185] . Compounds 2-5, 8-9, 12-15, 17-21, 23- 26, 28-30, 34-35, 37-41, 43-45, 48, 51-53, 58, 59, and 61 all showed anti-apoptotic activity by modulating these ...
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... of the PI3K/Akt pathway ameliorates apoptosis through the phosphorylation of GSK-3β by AKT [185][186][187]. Com- pounds 7, 19, 27, 30, 31, 35, 40, and 56 demonstrated anti-apoptotic activity by targeting the PI3K/Akt/GSK-3β pathway. ...
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... proteins (Sirt), and AMP-activated kinase (AMPK) [110,190,191]. PGC1α is a transcriptional factor that binds to Sirt3 promoters, interacting with Nrf2 to facilitate the upregulation of antioxidants [190]. Sirts can modulate the induction of several markers, such as PGC1α, to enhance the expression of antioxidant enzymes such as SOD [190,192,193] . Compounds 1, 3, 5, 10, 14, 18, 21-23, 27, 28, 30, 31, 36, 41, 43-46, 48, and 54 were reported to modulate the AMPK/ PGC1α/Sirt ...
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... addition to the biological activities earlier discussed, 33 compounds (1, 3-5, 7, 10, 15, 17, 22-24, 26-32, 39, 41, 43, 46-48, 51, 58, 59) were reported to increase ATP synthesis, 24 (4-7, 10, 11, 13, 14, 16, 17, 23, 24, 28, 30, 34-37, 41, 45, 46, 51, 55, 57) enhance the activity of mitochondria complexes, and 8 (1, 10, 11, 27, 29, 31, 43, 50) restore mitochondrial morphology. In addition to their reported antioxidant activity and increase in MMP, 7,8-dihydroxyflavone (6) and diphenyl diselenide (57) increased the level of mitochondrial complexes, while β-lapachone (47) improved ATP synthesis [141,154]. ...
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... addition to the biological activities earlier discussed, 33 compounds (1, 3-5, 7, 10, 15, 17, 22-24, 26-32, 39, 41, 43, 46-48, 51, 58, 59) were reported to increase ATP synthesis, 24 (4-7, 10, 11, 13, 14, 16, 17, 23, 24, 28, 30, 34-37, 41, 45, 46, 51, 55, 57) enhance the activity of mitochondria complexes, and 8 (1, 10, 11, 27, 29, 31, 43, 50) restore mitochondrial morphology. In addition to their reported antioxidant activity and increase in MMP, 7,8-dihydroxyflavone (6) and diphenyl diselenide (57) increased the level of mitochondrial complexes, while β-lapachone (47) improved ATP synthesis [141,154]. ...
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... addition to the biological activities earlier discussed, 33 compounds (1, 3-5, 7, 10, 15, 17, 22-24, 26-32, 39, 41, 43, 46-48, 51, 58, 59) were reported to increase ATP synthesis, 24 (4-7, 10, 11, 13, 14, 16, 17, 23, 24, 28, 30, 34-37, 41, 45, 46, 51, 55, 57) enhance the activity of mitochondria complexes, and 8 (1, 10, 11, 27, 29, 31, 43, 50) restore mitochondrial morphology. In addition to their reported antioxidant activity and increase in MMP, 7,8-dihydroxyflavone (6) and diphenyl diselenide (57) increased the level of mitochondrial complexes, while β-lapachone (47) improved ATP synthesis [141,154]. ...

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