Mitochondrial biogenesis
Encyclopedia
Mitochondrial biogenesis is the process by which new mitochondria are formed in the cell. Mitochondrial biogenesis is activated by numerous different signals during times of cellular stress or in response to environmental stimuli. 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 thought 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]
The master regulators of mitochondrial biogenesis appear to be the peroxisome proliferator-activated receptor gamma (PGC) family of transcriptional coactivators, including PGC-1α
, PGC-1β
, and the PGC-related coactivator, PRC. PGC-1α, in particular, is thought to be a master regulator. 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.
Mitochondria are produced from the transcription and translation of genes both in the nuclear genome and in the mitochondrial genome
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
. The majority of mitochondrial protein comes from the nuclear genome, while the mitochondrial genome encodes most parts of the electron transport chain
Electron transport chain
An electron transport chain couples electron transfer between an electron donor and an electron acceptor with the transfer of H+ ions across a membrane. The resulting electrochemical proton gradient is used to generate chemical energy in the form of adenosine triphosphate...
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]
The master regulators of mitochondrial biogenesis appear to be the peroxisome proliferator-activated receptor gamma (PGC) family of transcriptional coactivators, including PGC-1α
PPARGC1A
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha is a protein that in humans is encoded by the PPARGC1A gene....
, PGC-1β
PPARGC1B
Peroxisome proliferator-activated receptor gamma coactivator 1-beta is a protein that in humans is encoded by the PPARGC1B gene.-Further reading:...
, and the PGC-related coactivator, PRC. PGC-1α, in particular, is thought to be a master regulator. It is known to co-activate nuclear respiratory factor 2 (NRF2/GABPA)
GABPA
GA-binding protein alpha chain is a protein that in humans is encoded by the GABPA gene.-Interactions:GABPA has been shown to interact with Host cell factor C1, Sp1 transcription factor and Sp3 transcription factor.-External links:...
, and together with NRF-2 coactivates nuclear respiratory factor 1 (NRF1
NRF1
Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis,...
). The NRFs, in turn, activate the mitochondrial transcription factor A (tfam)
TFAM
Transcription factor A, mitochondrial is a protein that in humans is encoded by the TFAM gene.-Further reading:...
, 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.