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New insights intoexercise-inducedMitochondrial Adaptations
Mitochondria
Cristae Outer MembraneMatrix Inner MembraneLowell BB, and Shulman GI. Science 307: 384-387, 2005.Defects Parkinsons Alzheimerss Huntingtons Artherosclerosis Cardiomyopathies Diabetes
ADP + O2 ATP
Exercise-induced changes in mitochondrial content and mitochondrial respiration
Does antioxidant supplementation promote or impede skeletal muscle mitochondrial biogenesis?
Autophagy and exercise-induced mitochondrial biogenesis
Overview
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DefinitionsISEALMiller, K.L. (2012). Am J Physiol . 302: E496-499.Exercise: one-bout of exerciseTraining: a series of exercise boutsMitochondrial biogenesis: the making of new mitochondrial componentsit has been suggested that only measurements of the synthesis rates of mitochondrial proteins are indicative of mitochondrial biogenesis
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Mitochondrial adaptationsISEALGranata et al. 2016. FASEB J. 30(2): 959-970
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TerminologyISEALBishop, D.J., Skinner, T. (2014). Lactate Threshold. In: ESSA student manual for Health, Exercise and Sport Assessment.
Lactate inflection
Lactate threshold
8.51011.51314.51617.51920.5L1L2L3L4L5(HIT)
LILTL6(SIT)Wpeak
Terminology - LTISEALBishop, D.J., Skinner, T. (2014). Lactate Threshold. In: ESSA student manual for Health, Exercise and Sport Assessment.
L3L3L2L5
TerminologyISEALBishop, D.J., Skinner, T. (2014). Lactate Threshold. In: ESSA student manual for Health, Exercise and Sport Assessment.
TRTRUTUT
TerminologyISEALBaldwin et al. (2000). MSSE. 32:16481654.
Mitochondrial changes cross-sectionalISEALBishop et al. (2014). BBA. 140(4): 1266-1275.
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Changes in CS (rats) trainingISEAL
Bishop et al. (2014). BBA. 140(4): 1266-1275.
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Changes in CS trainingISEALTraining intensityTraining volumeBishop et al. (2014). BBA. 140(4): 1266-1275.
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Changes in CSISEAL
Granata et al. 2016. FASEB J. 30(2): 959-970
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Changes in CSISEALTraining intensity
Granata et al. 2016. FASEB J. 30(2): 959-970
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Changes in CSISEALTraining volume* Significantly different (P < 0.05) from NT, from RTGranata et al. (2016). FASEB J. In Press
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Changes in CSISEAL* Significantly different (P < 0.05) from pre-NT, # from post-NT
Training volumeGranata et al. (2016). FASEB J. In Press
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Changes in complexesISEAL
Granata et al. (2016). FASEB J. In Press
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Changes in CS (humans) trainingISEALTraining intensityTraining volume
Bishop et al. (2014). BBA. 140(4): 1266-1275.
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Changes in MR (mice) trainingISEALTraining intensityTraining volume
Bishop et al. (2014). BBA. 140(4): 1266-1275.
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ISEALGranata et al. (2015). FASEB J. in press
Changes in mitochondrial respiration
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ISEALIntensity & Mito RespirationDaussin, et al. (2008). Am J Physiol. 295: R264-272.
36%13%
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ISEAL
Changes in mitochondrial respirationGranata et al. (2015). In Review
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p160RIP140
v
PGC-1 mRNA
CREBMEF2PGC-1 AMPATP
AMPKPAMPKP
PGC-1
MEF2
Mito GenesNucleusPGC-1 PGC-1 p160
ROSp38 MAPKNRFp38PPP Thr ThrHDACPP Se SeNFATHDACRIP140p160PCaMK
PCalcineurinNFATP
T tubuleMuscle fibreAction potentialAxon terminalAchMotor end plateNa+K+Ca2+
Pp53
ISEALGranata et al. (2016) unpublished data
PGC-1 & p53 mRNA
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ISEALEdgett et al. (2013) PLOS ONE. 8(8): e71623
PGC-1 mRNA
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ISEALEdge et al. (2015) PLOS ONE. 10(12):e0141317
10 x 2 min intervals (90% VO2max, : 1 min rest).
Percival et al. (2015) JAP. 119(11): 1303-1312
PGC-1 mRNA
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Nuclear PGC-1ISEALGranata et al. (2016). Unpublished
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Effect of training statusISEALGranata et al. (2016). Unpublished
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ISEAL
p53
M
M
MDM2
PHF20
p53
M
Mnucleuscytosolstress
degradation
stability
MDM2
MDM2
PHF20 action on p53Cui et al. (2012). Nature Struct & Molec Biol 19, 916-924.
P53 and PHF20
30p53:The present study demonstrates that nuclear (and cytosolic) p53 protein content was increased immediately post-exercise, with no significant difference between the two exercise intensities.
A possible explanation for this concomitant increase may relate to an increase in p53 stability [39]. In this regard, p53 has been shown to have an extremely short half-life [47], and cellular stress has been reported to increase its half-life and stability [23, 28]. Consistent with these findings, p53 accumulation in both cellular pools may have been the result of an increased p53 stability in response to the increased physiological stress imparted to the cell by a single bout of exercise.
PHF20 (plant homeodomain finger-containing protein 20)
Given that our hypotheses is the exercise increases p53 stability, we investigated PHF20, a regulator of p53 that has been shown to increase p53 stability.How does this take place?In normal conditions p53 is bound to MDM2, which favours translocation outside the nucleus and its subsequent degradation by the proteasome.However, in condition of physiological stress (such as exercise) PHF20 moves inside the nucleus and binds to p53 reducing the p53-MDM2 interaction reducing p53 degradation and increasing p53 stability.
ISEAL
P53 and PHF20
Cui et al. (2012). Nature Struct & Molec Biol 19, 916-924.
31p53:The present study demonstrates that nuclear (and cytosolic) p53 protein content was increased immediately post-exercise, with no significant difference between the two exercise intensities.
A possible explanation for this concomitant increase may relate to an increase in p53 stability [39]. In this regard, p53 has been shown to have an extremely short half-life [47], and cellular stress has been reported to increase its half-life and stability [23, 28]. Consistent with these findings, p53 accumulation in both cellular pools may have been the result of an increased p53 stability in response to the increased physiological stress imparted to the cell by a single bout of exercise.
PHF20 (plant homeodomain finger-containing protein 20)
Given that our hypotheses is the exercise increases p53 stability, we investigated PHF20, a regulator of p53 that has been shown to increase p53 stability.How does this take place?In normal conditions p53 is bound to MDM2, which favours translocation outside the nucleus and its subsequent degradation by the proteasome.However, in condition of physiological stress (such as exercise) PHF20 moves inside the nucleus and binds to p53 reducing the p53-MDM2 interaction reducing p53 degradation and increasing p53 stability.
ISEAL
p53
Pnucleuscytosol
stabilityAMPKPp38P
P53 and PHF20Granata et al. (2016). Unpublished
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ConclusionsISEALExercise training volume key for mitochondrial content (citrate synthase)Exercise and training intensity key for mitochondrial respiration)May be related to exercise-dependent effects on nuclear PGC-1 and p53
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ISEALThanks
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