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. 2024 Dec 24;82(1):13. doi: 10.1007/s00018-024-05501-y

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

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Fig. 8 — TMAO suppressed UPR^mt, mitophagy, mitochondrial energetics, and mineralized matrix anabolism. GSK2606144 or nicotinamide riboside counteracted TMAO-induced losses of mRNA expression of UPR^mt marker, ATF5, Lonp1, ClpP, Hsp60, and Hsp10 (a) as well as suppression of protein levels of ATF5 and ubiquitinated ATF5 (b) and aggregated Aft5 (c). GSK2606144 or nicotinamide riboside preserved Pink1, Parkin, and LC3-II levels (d) and suppressed TMAO-induced losses of MitoTracker Green-staining of mitochondrial mass and Mitphay Dye/Lyso Dye-staining of mitophagic puncta formation (e); scale bar, 10 μm. GSK2606144 or nicotinamide riboside mitigated TMAO-induced suppression of mitochondrial basal, maximum, ATP-linked oxygen consumption (f), OXPHOS (g), ATP production, proliferation capacity (h), and mineralized matrix synthesis as well as osteogenic marker expression. Data are means ± standard errors calculated from a minimum 3 independent experiments, including immunoblotting. Asterisks (*) stand for significant difference (P < 0.01) analyzed by ANOVA test and post hoc Bonferroni test. GSK, GSK2606414; NR, nicotinamide riboside