Phagophore assembly site
Phagophore
Autophagosome
Lysosome
Autolysosome
Autophagy in Heart Disease Pathway
Nucleatione
Expansion
Phagophore
assembly
site
Phagophore assembly site
Completion
Phagophore
Autophagosome
Autophagosome
Phagophore
Phagophore assembly site
Phagophore
Nucleatione
Class 1
PI(3)K
Growth factor
deprivition
Autophagosome
Expansion
3-MA,
Wortmannin
Completion
ATG7
(E1)
ATG13
Autolysosome
Fusion Autolysosome
Lysosome
Autolysosome
Lysosome
Autolysosome
Lysosome
Autolysosome
Autolysosome
Fusion
ATG5
ATG10
(E2)
Degradation
Autolysosome
Degradation
ATG16
ATG1
Growth factor
PDK
Phagophore
Nucleatione
deprivition
Phagophore assembly site
Nutrient
deprivition
Phagophore assembly site
amino
acids
Phagophore
Elevated
afterload
mTOR
Nucleatione
Myocardial
Growth factor
infarction
AMPK
deprivition
AMP/
ATP
Nucleatione
Ischemia/
Nutrient
deprivition
reperfusion
Nucleatione
AKT
Expansion
amino
ROS
acids
PI(3)K
amino
acids
Growth factor
deprivition
and Nutrient
deprivition
AKT
Ischemia/
reperfusion
amino
acids
AKT
PDK
mTOR
TSC1/2
amino
amino
acids
acids
afterload
AKT
mTOR
Class 1
Myocardial
PI(3)K
Elevated
infarction
Elevated
Autophagy
eIFα
NucleusATG1
Kinase
Completion
ER
eEF2
ATP
Myocardial
Kinase Stress
Ischemia/
misfolded
AMPK
misfolded
RapamycinROS
AKT protein
infarction
protein
Ischemia/
reperfusion
misfolded
Myocardial
ROS
AMPK Autophagy
protein
reperfusion
AMP/
mTOR
Basal
AMP/
ATG6 (Vps34)
(Beclin)
ATG7
(E1)ATG15
ATG14
ClassATG6
III (PI3)K
eIFα (Vps34)
(Beclin)
Nucleus
ATG12
ATG14
PERK ATG6
Bcl-2
(Beclin)
Bcl-2
Nucleus
ATG4
Nucleus
PERK
Basal
ATG1
Cellular
homeostasis
ATG17
Basal
AMP/
ATP
ER
Stress
Rapamycin
misfolded
protein
Nucleus
ATG14
ATG6
(Beclin)
Autophagy
Bcl-2
Class III ATG4
(PI3)K
(Vps34)
ATG12
(LC3)
ATG12
ATG8
FusionATG7
ATG7
(LC3)
ATG8
(LC3)
ATG14
3-MA,
ATG4
Wortmannin
ATG10
ATG6
(E2)
(Beclin)
ATG15
ATG8
(LC3)
3-MA,
Wortmannin
Class III (PI3)K
ATG12
(Vps34)
ATG7
3-MA,
(E1)
ATG14
Wortmannin
Apoptosis
Bcl-2
ATG6
Apoptosis
(Beclin)
ATG7
(E1)
(E1)
(E1)
ATG8
(LC3)
ATG7
(E1)
ATG4
3-MA,
ATG5
Wortmannin
ATG8
(LC3)
ATG8
(LC3)
ATG12
ATG10
(E2)
Apoptosis
Fusion
3-MA,
Wortmannin
ATG3
(E2)
ATG7
(E1)
ATG5
ATG16
ATG3
ATG10(E2)
ATG12
ATG12
(E2)
ATG5ATG7
ATG10
(E2) (E1)
ATG12
ATG8
(LC3)
ATG3 ATG7
(E2)
ATG7
(E1)
(E1)ATG16
ATG8
(LC3)
ATG12
(E1)
ATG12
Degradation
ATG10
(E2)
(LC3)
ATG3
(E2)
ATG5
Degradation
ATG12
ATG12
ATG16
ATG5
Autolysosome
ATG5
ATG12
ATG3
ATG5
(E2)
ATG8
ATG12 ATG16
(LC3)
ATG12
ATG3
(E2)
ATG8
(LC3-II)
ATG8
(LC3)
ATG8
ATG8 (LC3-II)
Nucleus
(LC3)
ATG7 (LC3)
ATG3 Nucleus
ATG12
(E1) ATG12
(E2)
ATG7
Nucleus
(E1)
ATG5
ATG5
ATG16
ATG12
ATG8
(LC3-II) ATG12
ATG8
ATG5
(LC3-II)
ATG16
ATG8
(LC3)
ATG8
(LC3-II)
ATG3
ATG16
Nucleus
Nucleus
Excessive
ATG12
Cytoprotection
ATG10
Nucleus
(E2)
ATG8
Pathogenesis
Excessive
(LC3-II)
ATG16
Excessive
Pathogenesis
Pathogenesis
Pathogenesis
ATG12
ATG5
Excessive
ATG12
ATG5
ATG16
Apoptosis
ATG15
Cellular
eIFα
homeostasis
Basal
eEF2
Kinase
PERK
AMP/
ATP
Basal
ATG14
ATG4
Cytoprotection
ATG8
(LC3)
ATG6
(Beclin)
AMPK
ROS
Induced
Class III (PI3)K
(Vps34)
ER
Stress
ATG7
(E1)
ATG3
Excessive
ATG8
(LC3)
ATG8
(LC3)
ATG8
(LC3)
ATG7
(E1)
ATG3
(E2)
(E2)
Pathogenesis
ATG8
(LC3-II)
3-MA,
Wortmannin
Nucleus
misfolded
protein
Bcl-2
Cellular
homeostasis
Discover more at abcam.com/autophagy-heartdisease
Induced
Apoptosis
Cytoprotection
ATG16
ATG8
ATG5
(LC3)
ATG3
(E2)
Excessive
Pathogenesis
Legend:
ATG5
(E2)
Degradation
Cytoprotection
InducedATG7
ATG12
ATG12
ATG16
ATG5
ATG8
ATG8
ATG10 ATG3
Degradation
ATG3 ATG7ATG7
ATG10
(E1) (E1) ATG5 (LC3)
(E2) ATG5
(E2)(LC3)
(E2)
(E2)
ATG7
ATG16
(E1)
ATG8
ATG8
ATG8
Apoptosis
3-MA,
ATG12
Wortmannin
ATG16
ATG5
ATG12(LC3)
ATG8
ATG8
ATG8
ATG10
Cytoprotection (LC3)
Induced
Cytoprotection Excessive
(LC3)
ATG5 (LC3)
Cytoprotection
Bcl-2
Apoptosis
(E2)
ATG7
ATG3
(E1)
(E2)
Induced
Cellular
homeostasis
ATG7
(E1)
ATG12
(E1)
ATG10
ATG7
(E2)
ATG4
(E1)ATG8
ATG8
(LC3)
ATG15
ATG17
ATG12
Bcl-2
ATG8
CellularCellular
eIFα
3-MA, Basal
ATG7
Induced
(LC3)
Class III (PI3)K
homeostasis
homeostasis
Ischemia/ WortmanninBasal
ATG13
Cellular
misfolded
Induced
ROS
(E1)
(Vps34)
protein
homeostasis
reperfusion
PTEN
AMPK
ROS
ATG15
Autophagy
PERKClass III (PI3)K
eIFα
ER
ATG15
Stress
misfolded
protein
ATG14
ER
ATG17
StressPERK
Nucleus
ER
Stress
ATP
ROSATP
ATG1
Class III (PI3)K
ATG17
(Vps34)
eIFα
Autolysosome
ATG7
ATG7
(E1)
ATG1
ATG12
Fusion
ATG10
(E2)
ATG13
ATG12
ATG13
Autophagy
ATG13 PERK
mTOR
ER
PTEN AMP/
Stress eEF2
ATP
TSC1/2
Ischemia/
reperfusion
ATG15
AKT Rapamycin
PERK Rapamycin
mTOR
AMPK
AMP/
3-MA,
eEF2
Kinase
TSC1/2
TSC1/2
ATG4
ATG1
Autophagy
WortmanninATG17
3-MA,
Wortmannin
3-MA,
eEF2
Wortmannin
Kinase
AMPK
Lysosome
PTEN
Rapamycin
PDK eIFα
PTEN
ATG7
(E1)
ATG13
Rapamycin
Completion
ATG10
(E2) Fusion
ATG12
ATG17
Completion
3-MA,
Wortmannin
PTEN
ATG12
ATG10ATG12
ATG5
Autolysosome
(E2)
Degradation
TSC1/2
mTOR
Elevated
afterload,
Myocardial
infarction,
and Ischemia/
reperfusion
Class 1
PDK PI(3)K
Class 1
PI(3)K
TSC1/2
ATG12
ATG12
ATG7
ATG13 Autolysosome
Lysosome
(E1)
Fusion
ATG7
(E1)
ATG1
Completion
PTEN
Autophagy
Autophagosome
AKT
deprivition
Nutrient
deprivition
afterload
Myocardial
afterload
infarction
PDK
PDK
Expansion
Class 1
PI(3)K
amino
acids
3-MA,
ATG17
Wortmannin
Completion
Expansion
Rapamycin
Elevated
Expansion
afterload
Nutrient
NutrienteEF2
deprivition
deprivition
Kinase
Elevated
eEF2
Kinase
Myocardial
PDK
infarction
Class 1
Autophagosome
PI(3)K
Expansion
Nucleatione
Growth factor
Nutrient
deprivition
deprivition
GrowthTSC1/2
factor
deprivition
Growth factor
infarction
Elevated
Class 1
afterload
PTEN
Pathogenesis
MitochondrianCytoplasmic
macromolecule
ProteinOrganelle
aggregate
Phosphatidyl-Lysosomal
ethanolaminehydrolase
Autophagy is an evolutionarily conserved, lysosomal
pathway of engulfment, degradation and recycling of
cellular contents including long-lived proteins and
organelles. Autophagy promotes cell survival,
maintaining cellular homeostasis under resting and
stress conditions. Further, it plays a critical role in a
number of clinical disorders, including heart disease.
Autophagy is a complex process occurring in a
stepwise manner of several stages: nucleation,
expansion, and maturation/retrieval (see top scheme).
In the presence of growth factors and abundant
nutrients, class I PI(3)K kinase is activated through
insulin and insulin-like receptors and relays its signal to
AKT (see bottom scheme, left side). AKT, in turn,
stimulates a central regulator of autophagy, mTOR.
Activation of mTOR suppresses the autophagy pathway
and induces protein synthesis. However, in the
presence of diverse stimuli, including energy deprivation,
mTOR is inhibited, and autophagy is induced.
More than 30 AuTophaGy (ATG)-related proteins form
the core machinery of the autophagy pathway (see
bottom scheme, right side). The 3TG1 kinase complex
responds to upstream signaling from mTOR (ATG13/
ATG1/ATG17). The class III PI(3) kinase complex
mediates the nucleation of autophagosomes (Vps15/
Vps34/ATG14/ATG6). The two ubiquitin-like pathways of
ATG8 and ATG12 induce the expansion of the
phagophore. Various pharmacological intervention act
at different stages of the autophagy cascade (e.g. 3-MA,
Wortmannin, and Rapamycin).
Under basal conditions, autophagy helps to maintain
cellular homeostasis by scavenging long-lived proteins
and obsolete or defective organelles. Under stress
conditions, such as starvation or myocardial infarction,
autophagy enhances survival by intracellular ‘self-eating’
to replenish energy resources. However, excessive
autophagy can be detrimental due to uncontrolled
degradation of essential cytoplasmic materials, such as
mitochondria. Indeed, autophagy may contribute
importantly to the pathogenesis of heart disease under
certain conditions, including load-induced failure and
reperfusion after ischemia.
Produced in collaboration with Joseph A. Hill, Professor of Medicine and Molecular Biology, Chief in Division of Cardiology, UT Southwestern Medical Center.
Autophagy in Heart Disease Pathway
Antibody
Clonality
Applications
Host
Species Reactivity
Product Code
Akt1 (phospho S473)
P
ICC/IF, IHC-P, WB
Rb
Hu
Akt2
M
ELISA, ICC/IF, IHC-P, WB, sELISA
Ms
Hu, Ms, Rat, RecFrag
ab88058
Akt3
M
WB, ELISA, sELISA
Ms
Hu, Ms
ab89430
pan-Akt
P
ICC, IHC-P, WB
Rb
Hu, Ms, Rat; Predicted: Chk
AMPK alpha 1 + AMPK alpha 2
M
ELISA, ICC/IF, IHC-Fr, IP, WB
Ms
Hu, Ms, Rat, Dm; Predicted: Vert
ab80039
Apg10
P
WB
Rb
Hu; Predicted: Cow
ab79316
Apg12
P
WB, ELISA
Rb
Sc
Apg16
P
IHC-P, WB
Rb
Hu, Ms, ChHm, Hm
ab47946
Apg3
P
ICC/IF, WB
Rb
Hu; Predicted: Ms, Rat, Cow, Dog, Shp
ab66287
APG5L / ATG5
P
IHC-Fr, IHC-P, WB
Rb
Hu, Ms
ab64227
Apg7
M
Flow Cyt, ICC, IHC-P, IP, WB
Rb
Hu; Not reacting: Ms, Rat
ab52472
APG8A
P
WB
Rb
At
ab77003
ATG1 / ULK1
P
IHC-P, IHC-Fr, WB
Rb
Hu, Ms, Rat
ab65056
ATG4A
P
WB, ELISA
Rb
Hu
ab83290
ATG4B
P
ELISA, IHC-P, WB
Rb
Hu
ab70867
ATG4C
P
ELISA, ICC/IF, IHC-P, WB
Rb
Hu, Ms, AGMk
ab75056
ATG4D
P
IHC-P, IHC-Fr, WB
Shp
Hu, Ms
ab64736
ATG6 / Beclin 1
P
ICC/IF, IP, WB
Rb
Hu, Ms
ab16998
ATG8
P
ELISA, WB
Rb
Sc
ab4753
ATG9 / autophagy related protein 9
P
IHC-P, IHC-Fr, WB
Rb
Dm
ab74862
ATG9A
M
ELISA, ICC/IF, IHC-Fr, IP, WB
Hm
Hu, Ms, Rat
ab71795
ATG9B
P
IHC-P, IHC-Fr, WB
Shp
Hu
ab64775
Bcl2
P
ICC, IHC-Fr, IP, WB
Rb
Hu, Ms, Rat, Cow
eEF2 kinase / eEF2K
P
IHC-P
Rb
Hu, Ms
ab84756
eIF2 alpha (phospho S51)
M
Dot, ICC/IF, IHC-P, WB
Rb
Hu, Ms, Rat, AGMk, Dm, Predicted: Cow, Pig
ab32157
LC3A/B
P
ELISA, ICC/IF, WB
Rb
Hu, Ms, Rat, Chk, Chmp, Cow, Dog, Mk, Zfsh
ab58610
LC3B (HRP)
P
ICC/IF, IHC-Fr, WB
Rb
Hu, Ms
ab82554
LC3C
P
IHC-P, WB, IHC-Fr
Shp
Hu
ab62106
mTOR
P
ICC, IHC-Fr, IP, WB
Rb
Hu, Ms, Rat
ab2732
PDK1
P
ELISA, IHC-P, WB
Rb
Hu, Ms, Rat
ab31406
PDK2
M
Flow Cyt, ICC, IHC-P, WB
Rb
Hu; Not reacting: Ms, Rat
ab76152
PDK3
P
ELISA, WB
Rb
Hu; Predicted: Ms, Rat, Chk, Cow
ab80646
PDK4
P
IHC-P, WB, ELISA
Rb
Hu
ab71240
PERK
P
ELISA, IHC-P
Rb
Hu
ab77654
PI3 kinase p85 alpha
M
Flow Cyt, ICC/IF, IHC-P, IP, WB
Rb
Hu, Rat; Not reacting: Ms
ab40755
PTEN
M
ICC, IHC-Fr, IP, WB
Ms
Hu, Ms, Rat
ab79156
ClonalityApplications
P
ICC/IF, IP, WB
Host
Rb
Species cross reactivity
Hu, Ms
ab8805
ab4752
ab7973
Akt1 (phospho S473) (ab8932)
ClonalityApplications
P
ICC/IF, IHC-P, WB
Host
Species cross reactivity
RbHu
mTOR (ab2732)
ClonalityApplications
P
ICC, IHC-Fr, IP, WB
Host
Rb
Species cross reactivity
Hu, Ms, Rat
PDK1 (ab31406)
ClonalityApplications
P
ELISA, IHC-P, WB
Host
Rb
Species cross reactivity
Hu, Ms, Rat
Bcl2 (ab797)
ClonalityApplications
P
ICC, IHC-Fr, IP, WB
Host
Rb
Species cross reactivity
Hu, Ms, Rat, Cow
Copyright © 2013 Abcam. All Rights Reserved.
005-01/09-PW
Discover more at abcam.com/autophagy-heartdisease
ab8932
Beclin 1 / ATG6 (ab16998)
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Pr hli
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Related antibodies