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Mitochondrial biogenesis is the process by which cells increase their individual mitochondrial mass and copy number. Mitochondrial biogenesis is activated by numerous different signals during times of cellular stress or in response to environmental stimuli, such as aerobic exercise. The mitochondrion is a key regulator of the metabolic activity of the cell, and is also an important organelle in both production and degradation of free radicals. It is reckoned that higher mitochodrial copy number (or higher mitochondrial mass) is protective for the cell.
Mitochondria are produced from the transcription and translation of genes both in the nuclear genome and in the mitochondrial genome. The majority of mitochondrial protein comes from the nuclear genome, while the mitochondrial genome encodes most parts of the electron transport chain along with mitochondrial rRNA and tRNA. A major adaptation to mitochondrial biogenesis results in more mitochondrial tissues which increases metabolic enzymes for glycolysis, oxidative phosphorylation and ultimately a greater mitochondrial metabolic capacity.[Peter D. Wagner Summer 2011 Lecture]
PGC-1α, a member of the peroxisome proliferator-activated receptor gamma (PGC) family of transcriptional coactivators, is the master regulator of mitochondrial biogenesis. It is known to co-activate nuclear respiratory factor 2 (NRF2/GABPA), and together with NRF-2 coactivates nuclear respiratory factor 1 (NRF1). The NRFs, in turn, activate the mitochondrial transcription factor A (tfam), which is directly responsible for transcribing nuclear-encoded mitochondrial proteins. This includes both structural mitochondrial proteins as well as those involved in mtDNA transcription, translation, and repair.
- Valero T (2014). "Mitochondrial biogenesis: pharmacological approaches". Curr. Pharm. Des. 20 (35): 5507–9. PMID 24606795.
Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass . ... This work reviews different strategies to enhance mitochondrial bioenergetics in order to ameliorate the neurodegenerative process, with an emphasis on clinical trials reports that indicate their potential. Among them creatine, Coenzyme Q10 and mitochondrial targeted antioxidants/peptides are reported to have the most remarkable effects in clinical trials.
- Sanchis-Gomar F, García-Giménez JL, Gómez-Cabrera MC, Pallardó FV (2014). "Mitochondrial biogenesis in health and disease. Molecular and therapeutic approaches". Curr. Pharm. Des. 20 (35): 5619–5633. PMID 24606801.
Mitochondrial biogenesis (MB) is the essential mechanism by which cells control the number of mitochondria.
- Boushel R, Lundby C, Qvortrup K, Sahlin K (2014). "Mitochondrial plasticity with exercise training and extreme environments". Exerc Sport Sci Rev 42 (4): 169–74. doi:10.1249/JES.0000000000000025. PMID 25062000.
Exercise training stimulates mitochondrial biogenesis, yet an emerging hypothesis is that training also induces qualitative regulatory changes. ... The training-induced upregulation in mitochondrial volume and Vmax of respiration is well documented by morphological studies and functional observations at the level of single mitochondrial enzymes and whole mitochondria. In healthy humans, Vmax of mitochondrial oxidative phosphorylation (OXPHOS) is in excess of O2 delivery during whole-body exercise (5), and increases in VO2max with training are linked primarily to improved oxygen delivery and expansion of capillary volume, allowing for greater O2 diffusion (and extraction). Accordingly, there is strong evidence to support the hypothesis that, in healthy humans, muscle mitochondrial respiratory capacity poses no limitation to VO2max and always retains excess capacity over O2 delivery. However, changes in mitochondrial volume and regulation play a major role in enhancing submaximal endurance performance.
- Johri A, Chandra A, Beal MF (2013). "PGC-1α, mitochondrial dysfunction, and Huntington's disease". Free Radic. Biol. Med. 62: 37–46. doi:10.1016/j.freeradbiomed.2013.04.016. PMC 3722269. PMID 23602910.
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