[STUDY] PQQ Stimulates Mitochondrial Biogenesis by Activating SIRT1/PGC-1α

[nanonug]

COMMENT: I take PQQ as part of my cellular bioenergetics protocol (detailed here: From brain fog to clarity in 30 minutes) because I was aware of its effect on mitochondrial biogenesis but I didn't know about the molecular mechanism behind it. This study purportedly shows how PQQ enhances mitochondrial biogenesis. (PGC-1α is the master regulator of mitochondrial biogenesis.)

Abstract
Pyrroloquinoline quinone (PQQ), a redox-active o-quinone found in various foods and mammalian tissues, has received an increasing amount of attention because of a number of health benefits that can be attributed to its ability to enhance mitochondrial biogenesis. However, its underlying molecular mechanism remains incompletely understood. We have now established that the exposure of mouse NIH/3T3 fibroblasts to a physiologically relevant concentration of PQQ significantly stimulates mitochondrial biogenesis. The exposure of NIH/3T3 cells to 10-100 nM PQQ for 48 h resulted in increased levels of Mitotracker staining, mitochondrial DNA content, and mitochondrially encoded cytochrome c oxidase subunit 1 (MTCO1) protein. Moreover, we observed that PQQ treatment induces deacetylation of the peroxisome proliferator-activated receptor-γ-coactivator 1α (PGC-1α) and facilitates its nuclear translocation and target gene expression but does not affect its protein levels, implying increased activity of the NAD+-dependent protein deacetylase sirtuin 1 (SIRT1). Indeed, treatment with a SIRT1 selective inhibitor, EX-527, hampered the ability of PQQ to stimulate PGC-1α-mediated mitochondrial biogenesis. We also found that the PQQ treatment caused a concentration-dependent increase in the cellular NAD+ levels, but not the total NAD+ and NADH levels. Our results suggest that PQQ-inducible mitochondrial biogenesis can be attributed to activation of the SIRT1/PGC-1α signaling pathway by enhancing cellular NAD+ formation.​

 

[Learner1]

You might enjoy this too:

https://www.ncbi.nlm.nih.gov/m/pubmed/19448716/

Acute exercise initiates rapid cellular signals, leading to the subsequent activation of proteins that increase gene transcription. The result is a higher level of mRNA expression, often observed during the recovery period following exercise. These molecules are translated into precursor proteins for import into preexisting mitochondria. Once inside the organelle, the protein is processed to its mature form and either activates mitochondrial DNA gene expression, serves as a single subunit enzyme, or is incorporated into multi-subunit complexes of the respiratory chain devoted to electron transport and substrate oxidation.

The result of this exercise-induced sequence of events is the expansion of the mitochondrial network within muscle cells and the capacity for aerobic ATP provision.

 

[nanonug]

The result of this exercise-induced sequence of events is the expansion of the mitochondrial network within muscle cells and the capacity for aerobic ATP provision.

Yeap, exercise is (again) in my plans. I wasn't able to do much prior to dichloroacetate but I am at a point now that I am considering going back to play table tennis (which is the only type of exercise I enjoy.)

 

[Learner1]

There is no way I could tolerate table tennis at this point. I can lift weights and walk, though... Good luck with the table tennis!

 

[keenly]

Yes but there will also be oxidative stress with any mito supplement. Smoke with the fire.

 

[pattismith]

Both T4 and T3 increase MTCO1 as well,
and T3 increases SIRT1 and PGC-1α as well

Thyroid Hormones Enhance Mitochondrial Function in Human Epidermis
Journal of Investigative Dermatology, Volume 136, Issue 10, October 2016, Pages 1927

Since it is unknown whether thyroid hormones (THs) regulate mitochondrial function in human epidermis, we treated organ-cultured human skin, or isolated cultured human epidermal keratinocytes, with triiodothyronine (100 pmol/L) or thyroxine (100 nmol/L).

Both THs significantly increased protein expression of the mitochondrially encoded cytochrome C oxidase I (MTCO1), complex I activity, and the number of perinuclear mitochondria.

Triiodothyronine also increased mitochondrial transcription factor A (TFAM) protein expression, and thyroxine stimulated complex II/IV activity.

Increased mitochondrial function can correlate with increased reactive oxygen species production, DNA damage, and accelerated tissue aging. However, THs neither raised reactive oxygen species production or matrix metalloproteinase-1, -2 and -9 activity nor decreased sirtuin1 (Sirt1) immunoreactivity.
Instead, triiodothyronine increased sirtuin-1, fibrillin-1, proliferator-activated receptor-gamma 1-alpha (PGC1α), collagen I and III transcription, and thyroxine decreased cyclin-dependent kinase inhibitor 2A (p16ink4) expression in organ-cultured human skin.

Moreover, TH treatment increased intracutaneous fibrillin-rich microfibril and collagen III deposition and decreased mammalian target of rapamycin (mTORC1/2) expression ex vivo. This identifies THs as potent endocrine stimulators of mitochondrial function in human epidermis, which down-regulates rather than enhance the expression of skin aging-related biomarkers ex vivo. Therefore, topically applied THs deserve further exploration as candidate agents for treating skin conditions characterized by reduced mitochondrial function.