Mitochondria: Images and Insights for Researchers
Slides of the figures and other useful
images for
MITOCHONDRIA, THE BIG PICTURE:
A PRIMER FOR STUDENTS AND
RESEARCHERS
T
h
i
n
s
e
c
t
i
o
n
v
i
e
w
s
h
o
w
i
n
g
e
v
i
d
e
n
c
e
o
f
t
h
e
m
i
t
o
c
h
o
n
d
r
i
a
l
r
e
t
i
c
u
l
u
m
.
M
i
t
o
c
h
o
n
d
r
i
a
l
a
b
e
l
l
e
d
w
i
t
h
g
r
e
e
n
f
l
u
o
r
e
s
c
e
n
t
p
r
o
t
e
i
n
e
x
p
r
e
s
s
e
d
i
n
t
h
e
m
a
t
r
i
x
s
p
a
c
e
.
C
l
a
s
s
i
c
p
i
c
t
u
r
e
o
f
m
i
t
o
c
h
o
n
d
r
i
a
f
r
o
m
a
n
e
g
a
t
i
v
e
s
t
a
i
n
e
d
e
l
e
c
t
r
o
n
m
i
c
r
o
g
r
a
p
h
mamamm
matrix
Outer membrane
Inner boundary membrane
Intermembrane
space
Cristae membrane
micos
Intracristal space
Schematic showing the mitochondrial compartments
.
GLUCOSE
G6Pi
PYRUVATE
ACETYL CoA
CO
2
ATP
glycogen
ribose
5-Pi
nucleotides
lactate
amino acids
fatty acids
ketone bodies
sterols
hormones
Glycogen
storage
Gluconeogenesis
Glycolysis
Pentose Phosphate
Pathway
Urea Cycle
Pyruvate
Dehydrogenase
Complex
B
Oxidation
Oxidative
Phosphorylation
Citric Acid
Cycle
triacylglyercol
Fatty Acid Synthes
is
METABOLIC PATHWAYS INVOLVED IN GLUCOSE UTILIZATION
.
Boxed in yellow
are mitochondrial
pathways
S
h
o
r
t
t
e
r
m
C
e
l
l
u
l
a
r
C
o
n
t
r
o
l
o
f
E
n
e
r
g
y
M
e
t
a
b
o
l
i
s
m
G6Pi
pyruvate
acetyl CoA
ATP
Creatine Pi
Fatty Acid
Synthesis
Glycogen
Synthesis
Sterol
Synthesis
Triacylglyerol
Synthesis
AMP-activated Kinase
creatine
kinase
Acetyl-coA
carboxylase
glycogen
synthase
HMG-coA
reductase
GPAT
Fatty Acid
Oxidation
Pi
Pi
Pi
Pi
Pi
Mito/ER
contact
Mito
biogenesis/
OXPHOS/Kr
ebs cycle
Complex I/IV
AKT
SREBP
PGC1
alph
a
YY1
mTORC1
lipin
Lipid
synthesis
mTORC2
SIRT4
Glutaminolysis
GSK3
Glycolysis
mRNA
translation
4E-BP
eiF-4E
TFPAM
SK6
CAD
Nucleotide biosynthesis
PRPS2
ATG13
ULK
1
autophagy
mTOR: the master switch.
P38MAPK
active
CHOP
ATF2
ERK1/ERK2
(P42/44MAPK)
active
ASK1
inactive
AKT
active
apoptosis
autophagy
RAS
RAF
TRX
TRAFs
Ox Stress
p53
P
P
P
U
JNK
C-Jun
active
P
CHOP
P
mTOR
PI3K
STRESS SIGNALING AS EXEMPLIFIED BY OXIDATIVE STRESS.
PATHWAY OF FATTY ACID SYNTHESIS
citrate
M
i
t
o
c
h
o
n
d
r
i
a
l
A
c
e
t
y
l
C
o
A
l
i
p
o
a
t
e
elongated
saturated
fatty acids
unsaturated
fatty acids
palmitate
malonyl
CoA
ACC1
ACC2
Pi
P
i
p
i
malonyl
trnasferase
ACP
(complex I
A
T
P
c
i
t
r
a
t
e
l
y
a
s
e
C
Cytosolic
Acetyl CoA
Fatty acid
synthase
N
NADH
cytochrome b
reductase
Cytochrome b5
PATHWAY OF MITOCHONDRIAL FATTY ACID OXIDATION
unsaturated
F.A.
saturated
F.A.
acyl CoA
DH
’
s
acetyl CoA
short chain
enoyl-CoA
hydrolase
LCAD
VLCAD
SCAD
SCHA
D
ETF.Q
CPT1
CPT2
DECR
ETF
HADH
B
MCAD
ACAA2
Green fluorescence shows
labeled mitochondria, red
fluorescence is surface F1F0
reacted with an labeled
antibody to the enzymes
beta subunit.
Ectopic ATP synthase, shown for HepG2 cells.
M
i
t
o
c
h
o
n
d
r
i
a
l
i
n
v
o
l
v
e
m
e
n
t
i
n
a
p
o
p
t
o
s
i
s
.
Proteins in yellow are mitochondrial.
MCl1
Mcl-1
Ubiq
USP9X
Mule
NOXA
p53
FBW7
Release from
MOM
BIM
PUMA
Displaces
NOXA
c-Myc
Transcriptional regul.
Upregulates
NOXA
Promotes de-ubiq.
De-ubiquitinases
Ubiquitin ligase
A
p
o
p
t
o
s
i
s
:
r
e
g
u
l
a
t
i
o
n
o
f
t
h
e
l
e
v
e
l
s
o
f
t
h
e
a
n
t
i
-
a
p
o
p
t
o
t
i
c
p
r
o
t
e
i
n
M
c
l
-
1
.
mTOR
p38MAP K
SIRTs
AMPK
PGC-1alpha
PPARs
ERRs
CREB
NRFs
C
YY1
TCA enzymes
Fatty acid oxidation
Mitochondrial
biogenesis
ERRs = estrogen receptor related proteins
C
o
n
t
r
o
l
o
f
b
i
o
g
e
n
e
s
i
s
b
y
s
i
g
n
a
l
i
n
g
t
h
r
o
u
g
h
P
G
C
1
a
l
p
h
a
.
PGC-1alpha
PPARs
ERRs
NRFs
Fatty acid oxidation
Glucose metabolism
Mitochondrial
biogenesis
AMPK
SIRTs
mTOR
p38MAPK
REGULATION OF METABOLISM BY PGC-1ALPHA
GLUT4
ERRs = estrogen receptor related proteins
ATP/ADP/AMP
.
Where ATP is required for
transport.
METABOLITE
SHUTTLES
Citrate
Malate
Aspartate
Glutamate
Pyruvate
Acetyl CoA
Where membrane
potential/proton
gradient drives transport
Membrane
potential.
PROTEIN IMPORT/ADHERENCE etc
AND RELEASE.
Nfkappa B
,
BCl1,
PINK1,MCl1
AIF,Cytochrome c etc.
mtUPR
.
NADH/NAD+
NADPH/NADP+.
ROS/RNS.
Calcium
M
i
t
o
c
h
o
n
d
r
i
a
l
r
e
t
r
o
g
r
a
d
e
r
e
s
p
o
n
s
e
UPR proteins in mitochondria and endoplasmic reticulum.
HSP60
JNK
PATHWAY
C-JUN
PKR
eIF2alpha
PERK
Induces same
genes as
CHOP1
ATF4
Up reg of
CHOP1
Mitochondrial UPR (yellow)
ER UPR(blue
)
APOPTOSIS
INHIBITS PROTEIN
TRANSLATION
p38MAPK
HSP90
Up reg of
Heme Oxygenase
P
P
eIF2alpha
ATG13
P
(
1
:
5
,
0
0
0
)
M
i
t
o
c
h
o
n
d
r
i
a
l
d
i
s
o
r
d
e
r
s
;
(
e
.
g
.
,
m
i
t
o
c
h
o
n
d
r
i
a
l
D
N
A
d
e
p
l
e
t
i
o
n
s
y
n
d
r
o
m
e
s
)
(
1
:
1
0
,
0
0
0
)
F
a
t
t
y
a
c
i
d
o
x
i
d
a
t
i
o
n
d
i
s
o
r
d
e
r
s
i
n
c
.
m
e
d
i
u
m
-
c
h
a
i
n
a
c
y
l
-
C
o
A
d
e
h
y
d
r
o
g
e
n
a
s
e
d
e
f
i
c
i
e
n
c
y
(
1
:
2
0
,
0
0
0
)
(
1
:
1
5
,
0
0
0
)
P
h
e
n
y
l
k
e
t
o
n
u
r
i
a
(
1
:
1
5
,
0
0
0
)
M
e
t
h
y
l
m
a
l
o
n
i
c
a
c
i
d
u
r
i
a
.
M
e
t
h
y
l
m
a
l
o
n
y
l
-
C
o
A
m
u
t
a
s
e
,
c
o
b
a
l
a
m
i
n
m
e
t
a
b
o
l
i
s
m
(
1
:
4
0
,
0
0
0
)
A
m
i
n
o
a
c
i
d
o
p
a
t
h
i
e
s
(
1
:
5
0
,
0
0
0
)
P
e
r
o
x
i
s
o
m
a
l
d
i
s
o
r
d
e
r
s
;
e
.
g
.
,
Z
e
l
l
w
e
g
e
r
s
y
n
d
r
o
m
e
,
n
e
o
n
a
t
a
l
a
d
r
e
n
o
l
e
u
k
o
d
y
s
t
r
o
p
h
y
,
R
e
f
s
u
m
'
s
d
i
s
e
a
s
e
)
(
1
:
1
5
0
,
0
0
0
)
M
a
p
l
e
s
y
r
u
p
u
r
i
n
e
d
i
s
e
a
s
e
(
B
C
O
A
D
)
I
n
b
o
r
n
E
r
r
o
r
s
o
f
M
e
t
a
b
o
l
i
s
m
a
n
d
I
n
c
i
d
e
n
c
e
THE GENETICS AND PATHOLOGY OF MITOCHONDRIAL DISEASE
The Journal of Pathology
Volume 241, Issue 2,
pages 236-250, 2 NOV 2016 DOI: 10.1002/path.4809
http://onlinelibrary.wiley.com/doi/10.1002/path.4809/full#path4809-fig-0003
Images of skeletal muscle sections from a patient with a large scale
mtDNA delection showing ragged red fibers by Gomori and altered
levels of OXPHOS complexes.
Dive into the world of mitochondria with a collection of informative images showcasing aspects like mitochondrial reticulum, fluorescent protein labeling, electron micrograph views, and schematic diagrams of mitochondrial compartments. Learn about metabolic pathways, cellular energy control, mTOR signaling, and stress responses in a visual primer designed for students and researchers.
Download Presentation
Please find below an Image/Link to download the presentation.
The content on the website is provided AS IS for your information and personal use only. It may not be sold, licensed, or shared on other websites without obtaining consent from the author.If you encounter any issues during the download, it is possible that the publisher has removed the file from their server.
You are allowed to download the files provided on this website for personal or commercial use, subject to the condition that they are used lawfully. All files are the property of their respective owners.
The content on the website is provided AS IS for your information and personal use only. It may not be sold, licensed, or shared on other websites without obtaining consent from the author.
E N D
Presentation Transcript
Slides of the figures and other useful images for MITOCHONDRIA, THE BIG PICTURE: A PRIMER FOR STUDENTS AND RESEARCHERS
Thin section view showing evidence of the mitochondrial reticulum.
Mitochondria labelled with green fluorescent protein expressed in the matrix space.
Classic picture of mitochondria from a negative stained electron micrograph
Schematic showing the mitochondrial compartments. Outer membrane Inner boundary membrane matrix Intermembrane space mamamm Cristae membrane Intracristal space micos
GLUCOSE Glycogen storage Glycogen storage ribose 5-Pi G6Pi nucleotides glycogen Pentose Phosphate Pathway Glycolysis Gluconeogenesis Urea Cycle lactate PYRUVATE amino acids Pyruvate Dehydrogenase Complex B Oxidation fatty acids ACETYL CoA Fatty Acid Synthesis hormones sterols Oxidative Phosphorylation Citric Acid Cycle ketone bodies Boxed in yellow are mitochondrial pathways triacylglyercol CO2 ATP METABOLIC PATHWAYS INVOLVED IN GLUCOSE UTILIZATION.
Short term Cellular Control of Energy Metabolism AMP-activated Kinase Pi Pi Glycogen Synthesis glycogen synthase creatine kinase G6Pi Creatine Pi Pi pyruvate HMG-coA reductase Sterol Synthesis Pi Acetyl-coA carboxylase Fatty Acid Synthesis acetyl CoA Pi GPAT ATP Triacylglyerol Synthesis Fatty Acid Oxidation
mTOR: the master switch. mTORC2 mTORC1 lipin Lipid synthesis ATG13 AKT SREBP ULK 1 GSK3 4E-BP SIRT4 SK6 Glycolysis Glutaminolysis autophagy eiF-4E PGC1 alph a Mito biogenesis/ OXPHOS/Kr ebs cycle YY1 Mito/ER contact mRNA translation CAD PRPS2 TFPAM Complex I/IV Nucleotide biosynthesis
STRESS SIGNALING AS EXEMPLIFIED BY OXIDATIVE STRESS. Ox Stress RAS PI3K TRAFs TRX P RAF P AKT active U ASK1 inactive P JNK ERK1/ERK2 (P42/44MAPK) active P P C-Jun active P38MAPK active mTOR p53 ATF2 autophagy CHOP CHOP apoptosis
PATHWAY OF FATTY ACID SYNTHESIS Pi Mitochondrial Acetyl CoA CCytosolic Acetyl CoA ATP citrate lyase citrate ACC1 ACC2 p i P i ACP malonyl CoA (complex I Fatty acid synthase malonyl trnasferase palmitate Cytochrome b5 NNADH cytochrome b reductase lipoate elongated saturated fatty acids unsaturated fatty acids
PATHWAY OF MITOCHONDRIAL FATTY ACID OXIDATION DECR unsaturated F.A. saturated F.A. ETF CPT2 CPT1 MCAD SCAD VLCAD LCAD acyl CoA DH s short chain enoyl-CoA hydrolase HADH B ETF.Q SCHA D ACAA2 acetyl CoA
Ectopic ATP synthase, shown for HepG2 cells. Green fluorescence shows labeled mitochondria, red fluorescence is surface F1F0 reacted with an labeled antibody to the enzymes beta subunit.
Mitochondrial involvement in apoptosis. FasL? CELL? DEATH? Fas? FADD? CLEAVED? PARP? ER? stress? Caspase? 8? Cleaved? Casp3? procaspase3? Bid? Puma? bak? caspase7? p38MAPK? MCl1? Bim? Bcl-xL? mitochondria? BCl2? caspase9? AIF? Bad? p53? Noxa? bax? cytc? Apaf-1? nucleus? Aptosome? DNA? damage? Proteins in yellow are mitochondrial.
Apoptosis: regulation of the levels of the anti-apoptotic protein Mcl-1. Ubiquitin ligase Transcriptional regul. PUMA FBW7 c-Myc Ubiq Displaces NOXA MCl1 Mcl-1 NOXA De-ubiquitinases USP9X Promotes de-ubiq. BIM Release from MOM Mule Upregulates NOXA p53
Control of biogenesis by signaling through PGC1alpha. SIRTs mTOR AMPK p38MAP K PGC-1alpha CYY1 PPARs CREB NRFs ERRs Mitochondrial biogenesis TCA enzymes Fatty acid oxidation ERRs = estrogen receptor related proteins
REGULATION OF METABOLISM BY PGC-1ALPHA SIRTs mTOR AMPK p38MAPK PGC-1alpha PPARs ERRs GLUT4 NRFs Fatty acid oxidation Glucose metabolism Mitochondrial biogenesis ERRs = estrogen receptor related proteins
Mitochondrial retrograde response ATP/ADP/AMP. mtUPR . Where ATP is required for transport. METABOLITE SHUTTLES Citrate Malate Aspartate Glutamate Pyruvate Acetyl CoA NADH/NAD+ NADPH/NADP+. ROS/RNS. Calcium PROTEIN IMPORT/ADHERENCE etc AND RELEASE. Nfkappa B, BCl1, PINK1,MCl1 AIF,Cytochrome c etc. Where membrane potential/proton gradient drives transport Membrane potential.
UPR proteins in mitochondria and endoplasmic reticulum. JNK PATHWAY Induces same genes as CHOP1 C-JUN HSP60 Up reg of Heme Oxygenase P PKR p38MAPK P eIF2alpha INHIBITS PROTEIN TRANSLATION HSP90 eIF2alpha ATF4 Up reg of CHOP1 PERK ER UPR(blue) P Mitochondrial UPR (yellow) ATG13 APOPTOSIS
Inborn Errors of Metabolism and Incidence (1:5,000) Mitochondrial disorders; (e.g., mitochondrial DNA depletion syndromes) (1:10,000) Fatty acid oxidation disorders inc. medium-chain acyl-CoA dehydrogenase deficiency (1:20,000) (1:15,000) Phenylketonuria (1:15,000) Methylmalonicaciduria. Methylmalonyl- CoA mutase, cobalamin metabolism (1:40,000) Aminoacidopathies (1:50,000) Peroxisomal disorders; e.g., Zellweger syndrome, neonatal adrenoleukodystrophy, Refsum's disease) (1:150,000) Maple syrup urine disease (BCOAD)
THE GENETICS AND PATHOLOGY OF MITOCHONDRIAL DISEASE Images of skeletal muscle sections from a patient with a large scale mtDNA delection showing ragged red fibers by Gomori and altered levels of OXPHOS complexes. The Journal of Pathology Volume 241, Issue 2, pages 236-250, 2 NOV 2016 DOI: 10.1002/path.4809 http://onlinelibrary.wiley.com/doi/10.1002/path.4809/full#path4809-fig-0003
