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Genetics of fat cells hold the key to understanding muscle metabolic regulation. What did Puigserver et al (1998) state on the matter??.

PPAR-y and PGC-1a are responsible for the transition of white adipose tissue to brown adipose tissue (a more metabolic thermogenesis tissue) - concluding the PGC-1a is the master regulator of mt biogenesis (Lin et al, 2002)


Describe the Wu et al (1999) study and findings?

- Showed that overexpression of PGC-1a increases mitochondrial respiration and content in muscle cells(1.8x more at basal levels)

-this overexpression also increases mRNA and protein of key mitochondrial targets (e.g., cox1V, cytC)
- finally showed the importance of TF's for PGC-1a to increase mitochondrial biogenesis.


Calvo et al (2008) looked at muscle specific expression of PGC-1a, what did he find??

This improves ex performance and Vo2 max - with a much lower RER indicating better fat utilisation.

Also showed increases in mt gene expression - e.g. An increase in enzymes involved in FA oxidation/transport (e.g. CD36) and ox phosp (coxIV).

Finally showed increases in mt content and function in PGC-1a mOX mice (⬆️muscle glycogen, cytB, CS) indicating total mt biogenesis has occurred.


What did Baar et al (2002) demonstrate ?

An increase in PGC-1a mRNA and protein content in skeletal muscle following an acute bout of exercise.
- showing that PGC-1a gene expression is rapidly induced in human skeletal muscle before and after ex.


Building on from Baar's work, what did Pillegard et al (2003) find??

Looked at mRNA content of PGC-1a in untrained and trained legs in response to 3h of two-legged knee ext exercise.

PGC gene expression activation is higher in human skeletal muscle following high intensity ex

- also indicates the transient response of PGC-1a considering everything was back to normal at 24h.


What did Egan et al (2010) find regarding PGC-1a??

Showed an intensity dependent regulation of PGC-1a by a single bout of exercise
- after 3h, the high group are considerably higher (PGC mRNA abundance) than low intensity


What did Mathai et al (2008) find?

That the activation of PGC-1a gene expression following high int work is not affected by CHO ingestion.


What are the two critical TF's in activating PGC-1a?? (Irrcher et al, 2008)

MEF2 and CRE/ATF2 bind to promoter


What did akinomoto et al (2004) find regarding the activation of PGC-1a???

Showed that deletion of MEF2 or CRE/ATF2 blocks induction of PGC-1a consequently both are needed for transcription.


Discuss Wright et al (2007) and how PGC-1a initiates mitochondrial biogenesis ?

Ex induced mt biogenesis begins before the increase in muscle PGC-1a expression.

Exercise results in an increase in PGC-1a nuclear protein content, which suggests translocation to the nucleus from the cytosol is a pivotal first step in mt b.


What did Little et al (2011) find ??

An acute bout of high intensity interval training increases the nuclear abundance of PGC-1a and activates mt B in humans

MRNA expression of PGC-1a increases with a parallel increase in mitochondrial gene expression.
There was no acute Change in total PGC-1a protein content.


Discuss the Rowe et al (2012) study??

Demonstrated that PGC-1a is dispensable for ex induced mt biogenesis!

In PGC-1a KO mice , they showed a mild decrease in voluntary wheel performance. These mice also showed an induction of OX-phosp genes and activated mt b despite having no PGC-1a.
They also showed intact ETC activity (complex 3/4/5) in response to exercise