2 Cell ???, ??MONTH?? ??DATE??, 200? ©200? Elsevier Inc. DOI XXXXXXXXX See online version for ???

SnapShot: XXXXXXXXXXXXXXXXAUTHOR XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXAFFILIATION XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX

Changes in mRNA expression and protein content

HoursAcute exercise Chronic exercise trainingDays Weeks Months

mRNA

Protein content, enzyme function

Changefrombaseline

Improved exercise performanceand whole-body metabolism

PA

Exosomes

N U C L E U S

S A R C O P L A S M

C A P I L L A R Y

M I T O C H O N D R I O N

FAK CaMKII AMPK

Adaptiveresponses:

Hypertrophy

Mitochondrial biogenesis

SIRTsp38, ERK1/2, JNK

Angiogenesis

ERRα HIF-1α

HIF-1βPGC-1α

VEGF

MyoD

Myogenesis

MyoG

MRFs

MEF2

PGC-1β

Transcriptional regulatorsand mitochondrial genes

ERRαNRF-1/2PPARs

PRCPGC-1α

PHDs

miR-1, -133a, -133b, -181a, miR-9, -23a, -23b, -31

mTOR

Proteintranslationinitiation

p70S6K 4E-BP1

Autophagy

TORC1 TORC2

Akt

Contraction-induced modulators of gene expression in skeletal muscle

PiO2

NAD+:NADH

AMP:ATP

Mechanical stress

[Ca2+]i

Mechanosensation

Sarcolemmal disruption

Stimulus Sensor Downstream effectorPHDs

SIRTs

AMPK

MAPKs

CaMKs

FAK

PA

HIF-1α

PGC-1α, FOXO1, p53

HDAC, PGC-1α, CREB, SIRT1, HIF-1α

PGC-1α, CREB, ATF2

HDAC, CREB, SRF

mTOR, p70S6K

Akt, mTOR, FOXO1

Sources of energy provision in skeletal muscle

ATP hydrolysis

ATP resynthesis

Anaerobic pathways:Phosphocreatine degradation

Adenylate kinase reactionAnaerobic glycolysis

Aerobic pathways:Carbohydrate oxidation

Lipid oxidation

ATP + H2O ADP + Pi + H+ + energy

ADP + PCr + H+ ATP + Cr

Glycogen + 3 ADP 2 lactate + 2 H+ + 3 ATP

Palmitate + 23 O2 + 130 ADP + 130 Pi 16 CO2 + 146 H2O + 130 ATP Glucose + 6 O2 + 38 ADP + 38 Pi 6CO2 + 6H2O + 38 ATP

2ADP ATP + AMP

HDACHDAC

Glucose metabolism

PGC-1α

MEF2 CREB GEF

PRIP140

Lipid metabolism

PGC-1α

ERRα FOXO1 PPARs

Atrogenes

FOXOsMurFMAFbx

FFA

FFA

Lipolysis

Glycolysis

ATP-PCr

Autocrine/paracrinesignaling

FFA

PYR

ATP

ATP

FA-CoA

mtDNATfam

ADP

Ac-CoA

ATP

H+

H+

H+

H+

Electrontransportchain

NAD+, FAD,ADP+Pi

NADH, FADH2,ATP, CO2

I

II

III

IV

V

FABP

CD36

β-oxidation

TCAcycle

CPT1

Glucose

LAC

NADHNAD+

Glucose

HK

LDH

PDH

G-6-P G-1-P

GLUT4

ATP

ADP

Inter-organ communication

Liver

Adipocytes

Brain

Bone

MuscleSecreted factors: IL-6, IL-15, myostatin, BAIBA, lactate, exosomes, and others

Glycogen

GSPHOS

IMTG

SnapShot: Exercise MetabolismBrendan Egan,1 John A. Hawley,2 and Juleen R. Zierath3

1School of Health and Human Performance, Dublin City University, Glasnevin, Dublin 9, Ireland2Mary MacKillop Institute for Health Research, Centre for Exercise and Nutrition, Australian Catholic University, Melbourne, VIC 3000, Australia3Department of Molecular Medicine and Surgery and Department of Physiology and Pharmacology, Section of Integrative Physiology, Karolinska Institutet, 17177 Stockholm, Sweden

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