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Discuss Chen et al (2003)??

Demonstrated that AMPK activity is highly sensitive to the intensity of endurance exercise in human skeletal muscle
- for both AMPK kinase activity and ACCB phosphorylation were both related to intensity.


What did Egan et al (2010) find?

Showed a strong correlation between the activation of AMPK and PGC-1a mRNA abundance immediately after and during recovery (+3h and +19h) from isocaloric ex bouts
-showing AMPK is turned on immediately with exercise


What did De Bock et al (2005) show when looking at exercise in the fasted state?

It facilitates fibre-type specific intramyocellular lipid breakdown and stimulates glycogen resynthesis in humans.

Increased metabolic stress (in this case following ex in fasted state), leads to increases AMPK phosphorylation during exercise. - sig greater AMPK-thr172 phosphorylation post ex in fasted compared to CHO


How did Zong et al (2002) show AMPK is required for mitochondrial biogenesis in response to chronic energy deprivation ?

Using GPA, an energy restriction mimetic.

GPA increases PGC-1a mRNA expression, mitochondrial DNA and mitochondrial density in an AMPK dependent manner.


Garcia - Roves (2008)used a genetic mouse model to increase AMPK activity, what did he find??

Showed Mt b is increased in Tg-AMPKy3225Q mice, alongside showing increased mitochondrial density (⬆️MFN2⬆️OPA-1⬆️DRP-1) in these mice


What did O'neill et al (2011) show when KO of the b subunit??

This results in dramatic reductions in ex tolerance (speed ⬇️distance ⬇️) - these AMPKB1,B2M-KO mice also have reduced mitochondrial biogenesis


What did Mcgee and Hargreaves (2004) suggest regarding AMPK and HDAC5??

During exercise, HDAC5 is translocated from the nucleus (meaning less association with MEF2 allowing it to bind to PGC-1a) following phosphorylation by AMPK.

HDAC5 is a negative regulator of MEF2.


What did Jäger et al (2007) find??

States that AMPK phosphorylates and activates PGC-1a. This PTM is said to stabilise the PGC-1a protein allowing it to be more active and translocate to nucleus from cytosol.


What did Houtkooper et al (2012) find?

Stated that localisation and activity determine sirtuin function
-most important is SIRT1 that resides in the nucleus and cytosol and performs deacetylation on many targets (e.g. PGC1a)


Discuss Tuessenbaum et al (2001) ?

Discovered that an increased dose of SIR-2 (a homologe of SIRT1) prolongs lifespan in C.elegans


What did Bordone et al (2007) find??

Found that SIRT1 transgenic mice show phenotype resembling caloric restriction
- overexpression of SIRT1 improves glucose responsiveness and aerobic capacity


Discuss the STAC studies by Lagouge et al (2006) and Milne et al (2007)??

Lagouge - showed resveratrol (activates SIRT1) improves mitochondrial function and protects against metabolic disease
by activating SIRT1 and PGC1a

Milne et al (2007) identified STACs as potential therapeutics for the treatment of T2D


What did Dominy et al(2011) find ?? See diagram

SIRT1 improves mitochondrial function by activating PGC-1a and mediating effects on MT B


Discuss Gurd et al (2011)??

Showed that acute endurance exercise results in activation of nuclear SIRT1 and induction of MT B

The main effect of exercise training appears to be an increase in Nuclear SIRT1 activity, which coincides with an increase in nuclear PGC-1a content


Discuss Koltai et al (2010) ??

Showed that exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats.

Ageing increases global acetylation in rat SM which is reversed by exercise.
Increased acetlyation is associated with decreased NAD+ (i.e.
no ex)and reduced SIRT1 activity in old skeletal muscle


What did Seysell et al (2014) find?

Showed that ingesting a high fat diet for one month increases PGC-1a acetylation in parallel to decreased NAD+ in young human sm.


What did De bock et al (2008) find?

Looked at the effect of training in the fasted state on metabolic responses during exercise with CHO intake.

Found that exercise activation of Ffa transport and utilisation genes were increased to a greater extent in the fasted group.
Also, an increased abundance of proteins involved in FFA and glucose metabolism post training in the fasted exercise group.


What did De Lange et al (2007) conclude??

Proposed AMPK was a metabolic sensor in skeletal muscle in response to fasting - AMPK phosphorylation peaks @ 6 hours. Amp - 12 h, serum FFA -24h