My talk from our symposium "New insights into exercise-induced Mitochondrial Adaptations" at the acsm meeting in Boston, 2016

1. New insights into
exercise-induced
Mitochondrial Adaptations

2. Mitochondria
Cristae
Outer
Membrane
Matrix
Inner
Membrane
Lowell BB, and Shulman GI. Science 307: 384-387, 2005.
Defects 
o Parkinson’s
o Alzheimers’s
o Huntington’s
o Artherosclerosis
o Cardiomyopathies
o Diabetes
ADP + O2  ATP

3. 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

4. DefinitionsISEAL
Miller, K.L. (2012). Am J Physiol . 302: E496-499.
• Exercise: one-bout of exercise
• Training: a series of exercise bouts
• Mitochondrial biogenesis:
• the making of new mitochondrial components
• it has been suggested that only measurements of the synthesis
rates of mitochondrial proteins are indicative of mitochondrial
biogenesis

5. Mitochondrial adaptationsISEAL
Granata et al. 2016. FASEB J. 30(2): 959-970

6. TerminologyISEAL
Bishop, D.J., Skinner, T. (2014). Lactate Threshold.
In: “ESSA student manual for Health, Exercise and Sport Assessment”.
0
2
4
6
8
10
12
14
16
18
20
8.5 10 11.5 13 14.5 16 17.5 19 20.5
Treadmill Speed (km/h)
[lactate]
Lactate inflection
Lactate threshold

7. 0
2
4
6
8
10
12
14
16
18
20
[lactate]
Treadmill Speed (km/h)
8.5 10 11.5 13 14.5 16 17.5 19 20.5
L1
L2
L3
L4
L5
(HIT)
LI
LT
L6
(SIT)
Wpeak
Terminology - LTISEAL
Bishop, D.J., Skinner, T. (2014). Lactate Threshold.
In: “ESSA student manual for Health, Exercise and Sport Assessment”.

8. 0
5
10
15
20
25
50 55 60 65 70 80 90 100
% VO2max
[lactate]
High LT
Low LT
L3
L3L2
L5
TerminologyISEAL
Bishop, D.J., Skinner, T. (2014). Lactate Threshold.
In: “ESSA student manual for Health, Exercise and Sport Assessment”.

9. TR TR UTUT
TerminologyISEAL
Baldwin et al. (2000). MSSE. 32:1648–1654.

11. Mitochondrial changes – cross-sectionalISEAL
Bishop et al. (2014). BBA. 140(4): 1266-1275.

12. Changes in CS (rats) – trainingISEAL
R² = 0.0063
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60
CitrateSynthaseChange(%)
Training Intensity (m/min)
R² = 0.8753
0
10
20
30
40
50
60
70
80
90
100
0 5000 10000 15000 20000 25000
CitrateSynthaseChange(%)
Training Volume (m/wk)
Bishop et al. (2014). BBA. 140(4): 1266-1275.

13. Changes in CS – trainingISEAL
Training intensity Training volume
R² = 0.797
0
10
20
30
40
50
60
70
80
0 50000 100000 150000 200000 250000 300000
ChangeincitrateSynthaseactivity(%)
Training Volume
R² = 0.1097
0
10
20
30
40
50
60
70
80
0 50 100 150 200 250 300
Changeincitratesynthaseactivity(%)
Training Intensity (%VO2max)
Bishop et al. (2014). BBA. 140(4): 1266-1275.

14. Changes in CSISEAL
Granata et al. 2016. FASEB J. 30(2): 959-970

15. Changes in CSISEAL
Training intensity
Granata et al. 2016. FASEB J. 30(2): 959-970

16. Changes in CSISEAL
Training volume
* Significantly different (P < 0.05) from NT, † from RT
Granata et al. (2016). FASEB J. In Press

17. Changes in CSISEAL
* Significantly different (P < 0.05) from pre-NT, # from post-NT
Training volume
Granata et al. (2016). FASEB J. In Press

18. Changes in complexesISEAL
Granata et al. (2016). FASEB J. In Press

19. Changes in CS (humans) – trainingISEAL
Training intensity Training volume
R² = 0.797
0
10
20
30
40
50
60
70
80
0 50000 100000 150000 200000 250000 300000
ChangeincitrateSynthaseactivity(%)
Training Volume
R² = 0.1097
0
10
20
30
40
50
60
70
80
0 50 100 150 200 250 300
Changeincitratesynthaseactivity(%)
Training Intensity (%VO2max)
Bishop et al. (2014). BBA. 140(4): 1266-1275.

20. Changes in MR (mice) – trainingISEAL
Training intensity Training volume
R² = 0.7421
0
5
10
15
20
25
30
35
40
45
0 10 20 30 40 50
VmaxChange(%)
Training Intensity (m/min)
R² = 0.1364
0
5
10
15
20
25
30
35
40
45
0 2000 4000 6000 8000 10000 12000 14000
VmaxChange(%)
Training Volume (m/wk)
Bishop et al. (2014). BBA. 140(4): 1266-1275.

21. ISEAL
Granata et al. (2015). FASEB J. in press
Changes in mitochondrial respiration

22. ISEAL Intensity & Mito Respiration
Daussin, et al. (2008). Am J Physiol. 295: R264-272.
↑36%
↑13%

23. ISEAL Changes in mitochondrial respiration
Granata et al. (2015). In Review

24. p160
RIP
140
v
PGC-1α mRNACREBMEF2 PGC-1α
AMPATP
AMPK
P AMPK
P
PGC-1α
MEF2
Mito
Genes
Nucleus
PGC-1α
PGC-1α
p160
ROS p38 MAPK
N
R
Fp38
P P PThr Thr
HDAC
P PSe Se
NFAT
HDAC
RIP140
p160
P
CaMK
P
Calcineurin
NFAT
P
T tubule
Muscle fibre
Action potential
Axon terminalAch
Motor end plate
Na+
K+
Ca2+
P
p53

25. ISEAL
Granata et al. (2016) unpublished data
PGC-1α & p53 mRNA

26. ISEAL
Edgett et al. (2013) PLOS ONE. 8(8): e71623
PGC-1α mRNA

27. ISEAL
Edge 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-1α mRNA

28. Nuclear PGC-1αISEAL
Granata et al. (2016). Unpublished

29. Effect of training statusISEAL
Granata et al. (2016). Unpublished

30. ISEAL
p53 M
M
MDM2
PHF20
p53 M
M
nucleus
cytosol
stress
degradationstability
MDM2 MDM2
PHF20actiononp53
Cui et al. (2012). Nature Struct & Molec Biol 19, 916-924.
P53 and PHF20

31. ISEAL P53 and PHF20
Cui et al. (2012). Nature Struct & Molec Biol 19, 916-924.

32. ISEAL
p53
P
nucleus
cytosol
stability
AMPK
P
p38
P
P53 and PHF20
Granata et al. (2016). Unpublished

33. ConclusionsISEAL
• Exercise 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-1α and p53

34. ISEAL Thanks
@BlueSpotScience
David.Bishop@vu.edu.au