Importance of aerobic (mitochondrial) enzyme activity for endurance performance Flashcards
ENDURANCE PART 1 (17 cards)
What is Mitochondrial Biogenesis?
Describes the adaptive response of mitochondria to physiological stimuli
What does complete mitochondrial biogenesis represent?
Complete MB represents an increase in mitochondrial number, function, and capacity = an expansion of the mitochondrial reticulum
How can we measure mitochondrial biogenesis?
Via altered gene, protein, enzyme and synthetic rates
Exercise is a potent stimulus for mitchondrial biogenesis
What are the effects of exercise on mitochondrial O2 uptake + respiratory enzyme activity in muscle?
Holloszy et al 1967 - compared to sedentary, runner have significantly greater TCA cycle enzymes with ETC enzymes also increased.
What is the relationship between aerobic exercise and mitochondrial enzymes?
Spina et al 1970 - enzymes increase in muscle in response to 7-10 days aerobic cycling exercise
Coyle et al 1985 - shows adaptation is reversible, rapid decrease in enzyme activity following detraining in humans
Is type and number of muscle fibres genetic?
Egan & Zierath 2013 - strong genetic component on type and number of muscle fibres, high variability
How is mitochondrial content regulated in skeletal muscle?
Process of fission + fusion
- fusion - increases mitochondrial mass
- fission - increases mitochondrial number
mitophagy (degradation) - weeds out mitochondria that are not functioning well
What proteins regulate fission and fusion?
Fusion - mfn1+mfn2
Fission - Fis1
During fission Drp1 binds complexes together
Balance between fission and fusion = important in understanding what regulates mitochondria.
What are the 3 processes in how endurance exercise leads to skeletal muscle adaptation?
SIGNAL - muscle contraction alters concentration of allosteric factors in skeletal muscle
SENSOR - energy sensing proteins respond to alterations in these factors initiating cellular metabolic process.
MEDIATOR - energy sensing proteins target specific transcriptional regulators of metabolism, leading to altered fibre type characteristics, mitochondrial biogenesis and vascularization.
What is the most important determinant of how much protein is made from a gene?
The amount of RNA made from a gene.
An increase or decrease in the amount of RNA produced from a specific gene will have important functional affects on the cell.
What is the promoter region?
Region of DNA that signals how much RNA will be made from the gene
What are transcriptional factors?
Proteins that bind to DNA and change the rate of transcription
What are co-activators?
Proteins that do not bind DNA, but adjust activity of transcriptional factors.
What are the main factors involved in transcriptional control?
- Activators
- Repressors
- Coactivators
- Basal factors
According to Egan and Zierath 2014 - when do transcriptional changes occur?
Transcriptional changes occur rapidly in the initial stages post-exercise
One of the first things that happens after actute exercise bout is a spike in mRNA of a specific gene. Later comes an increase in protein content and enzymatic function.
What are 5 ways to increase transcription?
1) make more of an activator (transcriptional factor)
2) make more of a co-activator
3) change the activity of an activator (TF)
4) relocate co-activator on repressor
5) Change activity of a co-activator or expressor
What work done by Puigserver et al 1998 showed the genetics of fat cells held the key to understanding muscle metabolic regulation?
Work involing brown adipose tissue linked the transcriptional co-activator PGC1-a with mitochondrial biogenesis
