Exploring Mitochondria: Images and Insights for Researchers
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.
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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
