Mitochondrial Energetics — References

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Parent Topic: Mitochondrial Energetics | References Hub: 01 - Foundations References MOC

Primary Literature & Landmark Studies

Citation: Robinson, M. M., Dasari, S., Konopka, A. R., Johnson, M. L., Manjunatha, S., Esponda, R. R., Carter, R. E., Lanza, I. R., & Nair, K. S. (2017). Enhanced protein translation underlies improved metabolic and physical adaptations to different exercise training modes in young and old humans. Cell Metabolism, 25(3), 581–592.
Identifiers: DOI: 10.1016/j.cmet.2017.02.009 (DOI · SciDB · Scholar) | PMID: 28273480 (PubMed · Europe PMC)
Study Design: 12-week randomized controlled trial in young (18–30 yrs) and older (65–80 yrs) sedentary adults ( $N = 72$ ) comparing high-intensity aerobic interval training (HIIT), resistance training (RT), and combined training using vastus lateralis biopsies, RNA-seq, quantitative proteomics, and high-resolution respirometry.
Key Quantitative Outcomes:
- HIIT increased ex vivo skeletal muscle mitochondrial oxidative phosphorylation capacity by 49% in young adults and 69% in older adults ( $p < 0.001$ ), reversing age-associated declines in mitochondrial protein synthesis and insulin sensitivity (+28%).

Citation: Singh, A., D’Amico, D., Andreux, P. A., Fouassier, A. M., Blanco-Bose, W., Evans, M., Aebischer, P., Auwerx, J., & Rinsch, C. (2022). Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults. Cell Reports Medicine, 3(5), 100633.
Identifiers: DOI: 10.1016/j.xcrm.2022.100633 (DOI · SciDB · Scholar) | PMID: 35584623 (PubMed · Europe PMC)
Study Design: 4-month randomized, double-blind, placebo-controlled trial in overweight middle-aged adults ( $N = 88$ , aged 40–64 years; 500 mg vs. 1,000 mg daily Urolithin A vs. placebo).
Key Quantitative Outcomes:
- Urolithin A significantly increased lower-limb hamstring skeletal muscle strength by 12.0% (500 mg, $p = 0.028$ ) and 9.8% (1,000 mg, $p = 0.039$ ), improved peak $VO_{2}$ and 6-minute walk distance at 1,000 mg, decreased plasma acylcarnitines and C-reactive protein, and significantly increased skeletal muscle PINK1/Parkin mitophagy and TCA/OXPHOS protein expression.

Citation: Mortensen, S. A., Rosenfeldt, F., Kumar, A., Dolliner, P., Filipiak, K. J., Pella, D., Alehagen, U., Steurer, G., Littarru, G. P., & Q-SYMBIO Study Investigators. (2014). The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC: Heart Failure, 2(6), 641–649.
Identifiers: DOI: 10.1016/j.jchf.2014.06.008 (DOI · SciDB · Scholar) | PMID: 25282031 (PubMed · Europe PMC)
Study Design: 2-year prospective, multicenter, randomized, double-blind, placebo-controlled trial ( $N = 420$ patients with moderate-to-severe heart failure receiving CoQ10 100 mg TID [300 mg/day] vs. placebo).
Key Quantitative Outcomes:
- Long-term CoQ10 supplementation reduced the primary 2-year endpoint of Major Adverse Cardiovascular Events (MACE) by 43% (15% vs. 26%; $HR = 0.50, 95% CI [0.32, 0.80], p = 0.003$ ), cardiovascular mortality by 43% ( $p = 0.026$ ), and all-cause mortality by 42% ( $10% vs. 18%, p = 0.018$ ).

Citation: Handschin, C., & Spiegelman, B. M. (2006). Peroxisome proliferator-activated receptor $γ$ coactivator 1 coactivators, energy homeostasis, and metabolism. Endocrine Reviews, 27(7), 728–735.
Identifiers: DOI: 10.1210/er.2006-0037 (DOI · SciDB · Scholar) | PMID: 17018837 (PubMed · Europe PMC)
Study Design: Comprehensive molecular endocrinology synthesis of PGC-1 $α$ and PGC-1 $β$ transcriptional coactivation networks.
Key Quantitative Outcomes:
- Mapped the transcriptional cascade whereby exercise-activated AMPK, SIRT1, and calcineurin/CaMK induce PPARGC1A (PGC-1 $α$ ), driving coordinated upregulation of nuclear- and mitochondrial-encoded OXPHOS subunits, fatty acid $β$ -oxidation enzymes, and reactive oxygen species (ROS) detoxifying enzymes (SOD2, GPx1).