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Flashcards in Mito Biogenesis 2 Deck (12):
1

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)

2

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.

3

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.

4

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.

5

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.



6

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

7

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.

8

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

MEF2 and CRE/ATF2 bind to promoter

9

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.

10

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.

11

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.

12

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