Fig 2: Effects of CIC on mitochondrial physiology of OS cells. U2OS cells were treated with melatonin, melatonin + ROCK activator and melatonin + ROCK inhibitor for 24 h. A Immunofluorescence of mitochondria in U2OS cells. Scale bar = 20 μm. B Western blot shows TOM20, COX4I1, ATP synβ, PGC1α, NRF1 and TFAM expressions. C mtDNA levels of U2OS cells. D Mitochondrial ATP production in U2OS cells. E Mitochondrial O2 consumption in U2OS cells. *P < 0.05 vs. control, #P < 0.05 vs. MT. Data are expressed as mean ± SD fold induction of three independent experiments relative to control

Fig 3: The effects of PSO on ADR-injured cardiomyocytes. (a) Cell viability of ADR-injured HL-1 cells. (b) Statistical graph of cell viability. (c) Apoptotic analysis of ADR-injured HL-1 cells. (d) Apoptotic rates of ADR-injured HL-1 cells. (e) Intracellular ROS of ADR-injured HL-1 cells. (f) Statistical graph of intracellular ROS. (g) LDH level of ADR-injued HL-1 cells. (h) Representative images of PPARγ, SIRT1, PGC-1α, Bcl2, Bax, Nrf2, NQO1, HO-1, NRF1, TFAM, and UCP2 detected by western blots. (i) Quantitative analysis of western blots normalized to β-actin. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 vs. the control group or ADR group; ns, nonsignificant.

Fig 4: A proposed model of the role of CAV-1 in disrupting the integrity of the BBB under HH. Hypoxia treatment in cerebrovascular endothelial cells upregulates CAV-1 transcription by activating NRF1, thereby inducing a redistribution of the membranous claudin-5. Claudin-5 is further endocytosed by CAV-1-composed caveolae, impairing the integrity and permeability of the BBB. Moreover, endothelial autophagy mediates the clearance of aggregated claudin-5 in the cytosol, leading to BBB disruption and triggering HACE

Fig 5: ALDH2 protects angiotensin II-induced hypertrophic response via Nrf1-FUNDC1-dependent pathway.a, b Correlation between ALDH2 and Nrf1 expression as well as FUNDC1 and Nrf1 in GTEx database; c Western blots of Nrf1, Nrf2, PFKP, LDHA, and β-actin in tissue (loading control) (n = 6 samples per group); d Western blots of ALDH2, FUNDC1, Nrf1, and β-actin (loading control) in NRCMs after transfection (n = 6 samples per group); e depiction of the putative Nrf1-binding site located at FUNDC1 promoter; f predicted potential Nrf1REs; g chromatin immunoprecipitation (ChIP) assay in NRCMs; h construction pGL3 luciferase reporter vector with FUNDC1 promoter; i luciferase assay in NRCMs (n = 6 samples per group); j schematic diagram depicting the role of α-LA in pressure overload-induced changes in ALDH2 and mitophagy. Pressure overload suppresses expression and activity of myocardium ALDH2, which participates in pressure overload-induced inhibition of mitophagy receptor FUNDC1 and LC3II. Besides, the beneficial effects of α-LA in pressure overload heart failure was mediated by a novel ALDH2–Nrf1–FUNDC1 signaling pathway in which procedure Nrf1 modulates the FUNDC1 expression via directly binding to the 5′ promoter of FUNDC1. Mean ± SEM, ***P < 0.001. Statistical analysis was carried out by a two-tailed Student’s t test analysis.