Introduction
Techniques in comparative proteomics of mitochondria (both gel-based and gel-free)
Gel-Based Techniques
Non-Gel Based Techniques: MudPIT and ICATs
Perspective on human disease and mitochondrial comparative proteomics
Organ | Disease (Researcher) | Analytical method | Major proteins identified | Functional distribution | Primary Significance | |
---|---|---|---|---|---|---|
Up-regulated
|
Down-regulated
| |||||
Nervous system
| ||||||
Alzheimer's disease (AD) (Lovell MA.) | ICAT, 2D-LC/MS/MS | ATP synthase alpha chain | OXPHOS | Cells undergoing Aß -mediated apoptosis increase synthesis of proteins essential for ATP production and efflux to maintain metabolic functions. | ||
Pyruvate kinase, M1 isozyme | glycolysis | |||||
Glyceraldehyde 3 phosphate dehydrogenase | energy production | |||||
Cofilin | control of actin polymerization/depolymerization | |||||
Na+/K + -transporting ATPase a-3 chain | ATP production | |||||
VDAC 1 and 3 | apoptosis | |||||
Dihydropyrimidinase- related protein-1 (DRP-1) | axon guidance, invasive growth and cell migration | |||||
Multiple sclerosis (MS) (Broadwater L.) | SELDI-TOF-MS | Cytochrome c oxidase subunit 5b (COX5b) | component of Complex IV of the electron transport chain | Proteins identified would be used as neuroprotective therapeutic targets for MS. | ||
Hemoglobin β-chain | oxygen transport | |||||
Myelin basic protein (MBP) | component of the myelin membrane in the CNS | |||||
Creatine kinase (CKB) | creatine metabolic process | |||||
Neural degeneration (Pienaar IS.) | 2DE, ESI-QUADTOF/MS | Protein disulfide isomerase (PDI) | folding | Alteration of mitochondrial function may contribute to the beneficial effects associated with statin use. | ||
Heat shock proteins | protein assembly and folding | |||||
Dehydrogenase antiporter | transportation | |||||
Alpha-internexin (NF66) | cell differentiation, morphogenesis of neurons | |||||
Protein-tyrosine receptor type F polypeptide interacting protein (PTPRF) | cell adhesion receptor | |||||
Neuronal-specific enolase (NSE) | energy metabolism | |||||
Variation in ATP synthase, D chain | energy metabolism | |||||
Alpha-enolase-1 (ENO1) | glycolysis, growth control, hypoxia tolerance and allergic responses | |||||
Guanine nucleotide-binding proteins (G-proteins) | signal transduction | |||||
Cardiovascular system
| ||||||
Ischemia-induced cardiac injury (Kim N.) | 2-DE, MALDI-TOF-MS | Prohibitin | cell cycle | Proteomic analysis provides appropriate means for identifying cardiac markers for detection of ischemia-induced cardiac injury. | ||
VDAC | apoptosis | |||||
Contractile dysfunction (Essop MF.) | 2D-PAGE, ESI-Q-TOF | ATP synthase D chain | OXPHOS | Decreased contractile protein levels may contribute to the contractile dysfunction of hearts from diabetic mice. | ||
Ubiquinol cytochrome-C reductase core protein 1 | electron transport | |||||
Electron transfer flavoprotein subunit α | electron transport | |||||
Liver disease
| ||||||
Acetaminophen (APAP) affected the liver (Ruepp SU.) | 2D-DIGE, MALDI-TOF-MS | HSP10 and HSP60 | protein assembly and folding | APAP toxicity was a direct action of its known reactive metabolite NAPQI, rather than a consequence of gene regulation. | ||
Heat shock 70 kDa protein 9, (GRP75) | transporters and channels | |||||
High-fat diet induces hepatic steatosis (Eccleston HB.) | 2D-IEF/SDS-PAGE | uMUP-VIII major urinary protein | pheromone communication (only in rodents) | HFD causes steatosis, alters NO metabolism, and modifies the liver mitochondrial proteome, thus, NO may play an important role in the processes responsible for NAFLD. | ||
Thiosulfate sulfurtransferase | cyanide detoxification, role in iron-sulfur centers, sulfane metabolism | |||||
3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMG-CoA synthase) | catalyzes the condensation of acetoacetyl CoA and acetone step in ketogenesis | |||||
Succinate dehydrogenase subunit a (SDH-A) | catalyzes the oxidation of succinate to fumarate, flavoprotein | |||||
ATP synthase F1 α and β subunits | OXPHOS | |||||
Skeletal muscl
e
| ||||||
Hypoxia-induced changes in rat skeletal muscle (De Palma S.) | 2D-DIGE, HPLC ESI-MS/MS | Hypoxia inducible factor 1 (HIF-1R) | transcription | In vivo adaptation to hypoxia requires an active metabolic switch. | ||
Pyruvate dehydrogenase kinase 1 (PDK1) | regulation of glucose metabolism | |||||
Mitochondrial dihydrolipoamide dehydrogenase | branched chain family amino acid catabolic process | |||||
Succinyl CoA ligase α chain | tricarboxylic acid cycle | |||||
Lifestyle on the aging alterations ( Alves RM.) | 2-DE, MALDI-TOF/TOF | NADH dehydrogenase [ubiquinone] 1 α subcomplex subunit 4 | oxidative phosphorylation | Lifestyle is a key modulator for preventing aging-induced protein expression and functionality in mitochondria. | ||
Creatine kinase | signal transduction | |||||
Superoxide dismutase [Mn], mitochondrial | redox |
Nervous System
Cardiovascular System
Cancer and Hematological Diseases
Disease | Cell lines/Treatment | Analytical methods | Up-regulated proteins | Down-regulated proteins | Functions | Primary significance |
---|---|---|---|---|---|---|
Hematologic diseases
| ||||||
AML
| NB4/camptothecin | 2-DE, MALDI-TOF/TOF | Far upstream element-binding protein-1 (FUBP1) | transcription, translation, and degradation of proteins | Provided new insights for systematically understanding the mechanisms of the camptothecin-induced apoptosis. | |
Heterogeneous nuclear ribonucleoprotein A1 (HNRPA1) | mRNA processing | |||||
Heterogeneous nuclear ribonucleoproteins C1/C2 (HNRPC) | modified with shift of pI and MW | |||||
26S protease regulatory subunit 6A (PSMC3) | degradation | |||||
Proteasome subunit alpha type (PSMA)-1, 2, 6 | degradation | |||||
Non-Hodgkin's lymphoma
| Raji/Adramycin | DIGE, LTQ-ESI-MS/MS | ATP synthase d chain, mitochondrial (ATPQ, ATP5H) | OXPHOS | Specific mitochondrial proteins were uniquely susceptible to alterations in abundance following exposure to ADR and carry implications for the investigation of therapeutic and prognostic markers. | |
Prohibitin (PHB) | cell cycle | |||||
Heat shock 70 kDa protein 9 precursor (HSPA9) | transporters and channels | |||||
Isoform 4 of Mitochondrial ATP-binding cassette sub-family B member 6 (ABCB6) | protein synthesis and degradation | |||||
Superoxide dismutase [Mn], mitochondrial precursor (SOD2) | redox | |||||
Other solid tumors
| ||||||
Osteosarcoma
| 143B/devoid of mitochondrial DNA | 2-DE, MALDI-TOF/MS | NADH-ubiquinone oxidoreductase 75 kDa subunit | respiratory complexes subunits | Demonstrates the pleiotropic effects of mtDNA alterations and also gives valuable markers for the study of the mitochondrial-cytosolic coordination. | |
Mitochondrial 28S ribosomal protein S2 | mitochondrial translation apparatus | |||||
Mitochondrial import inner membrane translocase subunit Tim9 | protein transport | |||||
Succinyl-CoA ligase (ADP-forming) beta-chain | energy production | |||||
Breast cancer
| ||||||
MCF-7/resistance to adriamycin accompanied by verapamil | 2-DE, QqTOF-ESI-MS/MS | Cofilin | control of polymerization/depolymerization of actin | Implications of the changes are considered with respect to drug resistance. | ||
CoproporphyrinogenIII(CPO) | heme biosynthesis | |||||
3.2 trans-enoyl CoA isomerase | fatty acid oxidation | |||||
Adenylate kinase 2 |
ATP, OXPHOS
| |||||
Renal cell carcinomas
| ||||||
UMRC2, 786-0 and RCC4/VHL (von Hippel Lindau)-defective | 2-DE, MS | Heat shock 70 kDa protein | transporters and channels | Increased expression of septin 2 is a common event in RCC and protein modification may also alter septin 2 function in a subset of tumors. | ||
10-formyltetrahydrofolate dehydrogenase | one-carbon metabolism | |||||
Phosphoribosylglycinamide formyltransferase | purine biosynthesis | |||||
Ubiquinol cytochrome c reductase complex core protein 2 | electron transport | |||||
Elongation factor 2 | protein biosynthesis | |||||
Phosphofructokinase isozyme C | glycolysis | |||||
Thioredoxin reductase | differentiation, electron transport | |||||
Septin 2 | cell cycle | |||||
Prostate cancer
| ||||||
LNCaP/somatostatin | VDAC1, VDAC2 | apoptosis | Somatos might be able to curb the progression of advanced prostate cancer. | |||
Peroxiredoxin 2 (PRDX2) | antioxidant activity | |||||
Translationally controlled tumor protein (TCTP) | calcium binding and microtubule stabilization. |