Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain
Abstract
:1. Introduction
2. Results
2.1. Sex Regulates Metabolism, Transcription and Organelle Localisation
2.2. Gonadectomy Impacts Cellular Functions, including Endocytosis, Translation and Carbon Metabolism
2.3. Multiple Pathways in Mitochondrial Metabolism Can Be Targeted with Tibolone
2.4. Two-Way Interactions of Sex-Associated Factors
2.4.1. Sex and Gonadectomy Interact to Regulate Nonsense-Mediated Decay and Metabolism
2.4.2. Sex–Tibolone Interactions Impact Complex 1 of the Electron Transport Chain
2.4.3. Gonadectomy and Tibolone Interact to Regulate Translation and Post-Translation-Associated Pathways
2.5. Three-Way Interaction of Sex, Gonads and Tibolone Implicate Connection to Respiration and Alzheimer’s Disease
2.6. Meta-Analysis for Enriched Functions amongst Proteins Impacted by Sex-Specific Factors Reveals Connection to Alzheimer’s Disease
2.7. NDUFA2, NDUFA7 and UQCR10 Are Regulated by Sex–Gonad–Tibolone Interactions with Relevance to Alzheimer’s Disease
3. Discussion
3.1. Functional Enrichment Analysis Reveals Altered Pathways Associated with Alzheimer’s Disease and the Electron Transport Chain
3.2. Complex 1 Proteins Are Regulated by Sex-Hormone Interactions
3.3. Complex 3 Protein UQCR10 Is Regulated by Sex-Hormone Interactions
3.4. Future Studies and Limitations
4. Materials and Methods
4.1. Model Preparation
4.2. Proteomic Dataset Production
4.2.1. Protein Processing for Proteomics
4.2.2. Analysis via Liquid Chromatography Coupled to TRIPLE-TOF Mass Spectrometry
4.2.3. Data Preparation
4.3. Bioinformatic Analysis
4.3.1. Functional Enrichment Mapping
4.3.2. Protein–Protein Interactions (PPI)
4.3.3. Pathway and Process Enrichment Analysis
4.4. Graphing
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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McGovern, A.J.; Arevalo, M.A.; Ciordia, S.; Garcia-Segura, L.M.; Barreto, G.E. Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain. Int. J. Mol. Sci. 2022, 23, 14754. https://doi.org/10.3390/ijms232314754
McGovern AJ, Arevalo MA, Ciordia S, Garcia-Segura LM, Barreto GE. Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain. International Journal of Molecular Sciences. 2022; 23(23):14754. https://doi.org/10.3390/ijms232314754
Chicago/Turabian StyleMcGovern, Andrew J., Maria Angeles Arevalo, Sergio Ciordia, Luis Miguel Garcia-Segura, and George E. Barreto. 2022. "Respirasome Proteins Are Regulated by Sex-Hormone Interactions in the Brain" International Journal of Molecular Sciences 23, no. 23: 14754. https://doi.org/10.3390/ijms232314754