How weight lifting increases mitochondria

Uguccioni G, Hood DA. The importance of PGC-1α in contractile activity-induced mitochondrial adaptations. Am J Physiol Endocrinol Metab. 2011 PMC free article


skeletal muscle has the ability to adapt to changes in metabolic demands by production of more proteins. Chronic contractile activity (CCA) is one of those metabolic demands. CCA results in production of more mitochondria. Only about 1% of the proteins in the mitochondria electron transport chain are coded for by mitochondrial DNA. The muscle must derive these transcripts from the chromosomal DNA in the nucleus. Prior to the featured study, peroxisome proliferator-activated receptor (PPAR)γ and its coactivator-1α (PGC-1α) were deemed critical to mitochondrial function, respiration, and biogenesis in skeletal muscle. Changes in PGC-1α mRNA correlated with changes in mitochondrial content as mesaured by cytochrome c oxidase (COX) activity. The scienific community had data from PGC-1α-knockout mice that were able to adapt to an exercise program and some contrasting data from animals with a muscle-specific deletion of PGC-1α. These authors used a contractile myotubule cell culture approach. To assess the role of PGC-1α they used silencing RNA to prevent the PGC-1α transcript from being translated into proteins.

The purpose of the electron transport chain is to transport electrons (yellow circles) from NADH and FADH2 to O2. H2O is the byproduct. H+ are pumped into the membrane space. Energy from this gradient is used to generate ATP. Complex IV contains 13 subunits. Cox IV contains two coppers and irons (Fe).

Some how or another CCA increases the protein levels of PGC-1α. We can hypothesize that this is somehow linked to ATP and its depletion by too much activity. PPAR)γ, PGC-1α and some other proteins increase the transcription of genes that code for mitochondrial proteins.


C2C12 murine skeletal muscle cells were proliferated in a nutrient rich medium containing some antibiotics and fetal bovine serum. When they became a bit crowded the fetal bovine serum was switched to adult horse serum. The result was myotubes that could contract in their comfy cell culture dishes.

Two platinum wire electrodes 2 cm apart were inserted into the culture dish. Myotubes were subjected to electrical stimulation at a frequency of 5 Hz and an intensity of 9 V chronically for 3 h/day over 4 successive days shortly after they differentiated. Myotubes were allowed to rest for 21 h after each bout of contractile activity. The changed the medium 1 hr before exercise. This Chronic Contractile Activity went on for four days, proteins and messenger RNA (mRNA) were extracted.


The cell culture model was validated by showing that CCA increased COX activity as well as O2 consumption. The silencing RNA was successful in decreasing PGC-1α mRNA levels to about 30% of the control.These results gave Uguccioni and Hood confidence in their model

CCA increased protein levels of mitochondrial transcription factor Tfam and cytochrome C. PGC-1α silencing slightly decreased protein levels in resting but not CCA myotubules. Chronic contracting seemed to overcome this deficiency. This was not the case for COX IV. Because the silencing of was not complete, Uguccioni and Hood were able to show a nice, linear correlation between PGC-1α mRNA and COX activity.

Chronic Contraction causes depletion of ATP and an increase it AMP. This activates autophosphorylation of AMPKinase. In addition to phosphorylating itself, PKA was shown to phosphorylate ACC which inhibits ACC and shifts the balance to acetyl CoA, which can be used by the mitochondria in the TCA cycle, which generates NADH and FADH to make ATP.

AMP protein kinase is an enzyme that communicates decreases in ATP (adenosine triphosphate) and subsequent increases in adenosine monophosphate (AMP). AMPK accomplishes this task by attaching a phosphate to proteins starting with itself. Other targets include acetyl-CoA carboxylase 1 (ACC1) factors related to glucose trasnportacross the cell membrane. According to UniProt, PGC-1α has two AMPK phosphorylation site: threonine 178 and serine 539. Knocking down PGC-1α with silencing RNA increased some of these phosphorylations. We can hypothesize the myotubules not expanding mitochondria like nature intended them to.


This is how weight lifting increases mitochondria. There seems to be a huge link to COX IV and PGC-1α. The body builder may want to consider a copper supplement and then an iron supplement as these are cofactors in COX IV. Copper comes before iron because copper is required to absorb iron. See the ceruloplasmin post. CopperOne is just a more natural copper supplement because it is in the +1 oxidation state just like the Cox17 chaperone that loads cytochrome C oxidase of complex IV with Cu+1.

Published by BL

I like to write educational websites

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