Hydroxytyrosol as a Mitochondrial Homeostasis Regulator: Implications in Metabolic Syndrome and Related Diseases
Abstract
:1. Introduction
2. The Regulatory Mechanisms of Hydroxytyrosol on Mitochondrial Homeostasis
2.1. Modulation of Hydroxytyrosol on Mitochondrial Fusion and Fission
2.2. Modulation of Hydroxytyrosol on Mitochondrial Biogenesis and Oxidative Phosphorylation
2.3. Modulation of Hydroxytyrosol on Mitophagy
2.4. Modulation of Hydroxytyrosol on Mitochodnria-Endoplasmic Reticulum Crosstalk
2.5. Modulation of Hydroxytyrosol on Gut Microbiota-Mitochondria Axis
3. The Protective Role of Hydroxytyrosol in Metabolic-Related Diseases
3.1. Type 2 Diabetes and Its Complications
3.2. Obesity, Hyperlipemia, and Nonalcoholic Fatty Liver
3.3. Hypertension-Related Diseases
4. Challenges and Future Perspectives
4.1. Direct Targets of Hydroxytyrosol: Awaiting Further Elucidation
4.2. Mitochondrial Delivery System for Enhanced Targeting
4.3. Synergistic Therapies for Boosting Efficacy
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
HT | Hydroxytyrosol |
MetS | Metabolic Syndrome |
T2DM | Type 2 Diabetes Mellitus |
NAFLD | Non-Alcoholic Fatty Liver Disease |
OXPHOS | Oxidative Phosphorylation |
ER | Endoplasmic Reticulum |
OPA1 | Optic Atrophy 1 |
Drp1 | Dynamin-Related Protein 1 |
Mfn2 | Mitofusin 2 |
PGC-1α | Peroxisome Proliferator-Activated Receptor γ Coactivator 1-α |
mtDNA | Mitochondrial DNA |
SIRT1 | Sirtuin 1 |
ROS | Reactive Oxygen Species |
HFD | High-Fat Diet |
MERC | Mitochondria–ER Contact |
UPR | Unfolded Protein Response |
eNOS | Endothelial Nitric Oxide Synthase |
ABPP | Activity-Based Protein Profiling |
TPP | Thermal Proteome Profiling |
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Model | Experimental Outcome | Ref. | |
---|---|---|---|
Antioxidant | MPP+-Induced Striatal Lipid Peroxidation in Rats model | HT increased GSH activity and GSH/GSSG ratio | [37] |
Anti-viral | Peripheral blood mononuclear cells isolated from healthy blood donors | Hydroxytyrosol inhibited HIV-1 infections in cell | [38] |
Antibacterial | Spectrum Beta-Lactamases | HT disrupted bacterial enzymes crucial for maintaining cell integrity and DNA replication | [39] |
Anti-cancer | breast cancer cell lines (MDA-MB-231, MDA-MB-468, and SUM159) colorectal cancer cell line (Caco-2) | HT modulated intracellular copper levels inhibited tumor progression HT increased Caco-2 cell DNA methylation, decreased EDNRA expression | [40] [41] |
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Xu, J.; Wei, H.; Sun, Z.; Li, W.; Long, J.; Liu, J.; Feng, Z.; Cao, K. Hydroxytyrosol as a Mitochondrial Homeostasis Regulator: Implications in Metabolic Syndrome and Related Diseases. Antioxidants 2025, 14, 398. https://doi.org/10.3390/antiox14040398
Xu J, Wei H, Sun Z, Li W, Long J, Liu J, Feng Z, Cao K. Hydroxytyrosol as a Mitochondrial Homeostasis Regulator: Implications in Metabolic Syndrome and Related Diseases. Antioxidants. 2025; 14(4):398. https://doi.org/10.3390/antiox14040398
Chicago/Turabian StyleXu, Jie, Huanglong Wei, Zhenyu Sun, Wankang Li, Jiangang Long, Jiankang Liu, Zhihui Feng, and Ke Cao. 2025. "Hydroxytyrosol as a Mitochondrial Homeostasis Regulator: Implications in Metabolic Syndrome and Related Diseases" Antioxidants 14, no. 4: 398. https://doi.org/10.3390/antiox14040398
APA StyleXu, J., Wei, H., Sun, Z., Li, W., Long, J., Liu, J., Feng, Z., & Cao, K. (2025). Hydroxytyrosol as a Mitochondrial Homeostasis Regulator: Implications in Metabolic Syndrome and Related Diseases. Antioxidants, 14(4), 398. https://doi.org/10.3390/antiox14040398