Mitochondrial biogenesis

Mitochondrial biogenesis is the process by which cells increase their individual mitochondrial mass and copy number.[1][2] Mitochondrial biogenesis is activated by numerous different signals during times of cellular stress or in response to environmental stimuli, such as aerobic exercise.[1][2][3] 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 mitochondrial 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 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. However, depending on the energy substrates available and the REDOX state of the cell, the cell may increase or decrease the number and size of mitochondria.[4] Critically, mitochondrial number and morphology varies according to cell type and context-specific demand, whereby the balance between mitochondrial fusion/fission regulates mitochondrial distribution, morphology, and function[5][4]

PGC-1α, a member of the peroxisome proliferator-activated receptor gamma (PGC) family of transcriptional coactivators, is the master regulator of mitochondrial biogenesis.[1][2][6] 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.

References

  1. 1 2 3 Valero, Teresa (2014). "Editorial (Thematic Issue: Mitochondrial Biogenesis: Pharmacological Approaches)". Current Pharmaceutical Design. 20 (35): 5507–9. doi:10.2174/138161282035140911142118. PMID 24606795.
  2. 1 2 3 Sanchis-Gomar, Fabian; Garcia-Gimenez, Jose; Gomez-Cabrera, Mari; Pallardo, Federico (2014). "Mitochondrial Biogenesis in Health and Disease. Molecular and Therapeutic Approaches". Current Pharmaceutical Design. 20 (35): 5619–33. doi:10.2174/1381612820666140306095106. PMID 24606801.
  3. ↑ Boushel, Robert; Lundby, Carsten; Qvortrup, Klaus; Sahlin, Kent (2014). "Mitochondrial Plasticity with Exercise Training and Extreme Environments". Exercise and Sport Sciences Reviews. 42 (4): 169–74. doi:10.1249/JES.0000000000000025. PMID 25062000.
  4. 1 2 Mishra, Prashant; Chan, David C. (2016). "Metabolic regulation of mitochondrial dynamics". The Journal of Cell Biology. 212 (4): 379–87. doi:10.1083/jcb.201511036. PMC 4754720Freely accessible. PMID 26858267.
  5. ↑ Bertholet, A.M.; Delerue, T.; Millet, A.M.; Moulis, M.F.; David, C.; Daloyau, M.; Arnauné-Pelloquin, L.; Davezac, N.; Mils, V.; Miquel, M.C.; Rojo, M.; Belenguer, P. (2016). "Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity". Neurobiology of Disease. 90: 3–19. doi:10.1016/j.nbd.2015.10.011. PMID 26494254.
  6. ↑ Johri, Ashu; Chandra, Abhishek; Flint Beal, M. (2013). "PGC-1α, mitochondrial dysfunction, and Huntington's disease". Free Radical Biology and Medicine. 62: 37–46. doi:10.1016/j.freeradbiomed.2013.04.016. PMC 3722269Freely accessible. PMID 23602910.

Further reading

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