The document discusses the effects of exercise on mitochondrial adaptations, highlighting the roles of training volume and intensity in promoting mitochondrial biogenesis and respiration. It references various studies and terminologies related to mitochondrial changes, such as citrate synthase activity and lactate threshold. Conclusively, it emphasizes the significant relationship between exercise characteristics and nuclear factors like PGC-1α and p53 in influencing mitochondrial content and function.

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