Scheffler Immo E. Mitochondria

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441

Mitochondria, Second Edition, by Immo E. Schefﬂ er

INDEX

a14α intron, 74

AAA protein family, 155

“Acceptor control” phenomenon, 234

Accessory proteins, 146–147

Acetyl-CoA, 299, 301, 305

Aconitase, 110, 301

Activator/repressor protein, 87

Active recombination system, 69–70

Active transport, ATP synthesis and,

173

Acyl-CoA/carnitine shuttle, 306

Acyl-CoA dehydrogenases, 308

Acyl species, in cardiolipin, 316

a cytochromes, 175

Adenine nucleotide carrier/transporter

(ANC/T), 262

Adenine nucleotide translocase (ANT),

331–332

Adenine nucleotide transporter (ANT),

334, 339, 340, 394

Adenylate kinase, 262

ADP (adenosine diphosphate)

“acceptor,” 234

ADP/ATP translocator, 331–334. See

also ATP/ADP entries

inhibitors in the puriﬁ cation of, 333

ADP + P

excess, 261

Aequorin, 338

Agaricus bitorquis, 72

Age-dependent mtDNA mutations, 382

Aging, mtDNA and, 377–389

ALA synthase, 310–312. See also

Aminolevulinate synthase

Aldol–Claisen condensation, 301

γ complex, 250–251

α-ketoglutarate dehydrogenase, 303

α-synuclein, 385

Alpha-tocopheryl succinate, 276

“Alternating” site model, 250

Alzheimer’s disease (AD), 384–385,

386–387

late-onset, 387

Aminolevulinate synthase, 92. See also

ALA synthase

β-Aminolevulinic acid (ALA), 310. See

also ALA synthase

AMP (adenosine monophosphate), 262

β-Amyloid precursor protein (APP),

386

effect on mitochondrial functions, 387

Amyotrophic lateral sclerosis (ALS),

389

442 INDEX

ATP/ADP carrier, 150. See also ADP/

ATP translocator

ATP/ADP exchange, 331

[ATP]/[ADP] ratio, 262, 264

ATPase6 peptide, 65

ATPase6 reading frame, 67

ATPase8 reading frame, 67

ATP binding, 250

sites of, 247

ATP-dependent proteases, 154–155

ATP-sensitive channel, 336

ATP synthase, 232, 236, 244–258

assembly and activity of, 258

cristae morphology and, 26

dimerization of, 258

mutations in, 371

subunit composition of, 246, 258

X-ray structure of, 247–249

ATP synthase mechanism, biochemical

observations related to, 252

ATP synthesis, 230

catalytic mechanisms and, 249–253

Atractyloside, 333, 334

(A+T)-rich intergenic sequences, 75

a-type cytochromes, 313–314

AUG initiation codon, 122

Autophagy, 54

Autosomal dominant mutations, 386

avUCP, 270

Axons, movement of mitochondria in, 35

Bacillus subtilis, 199

Bacterial chaperones, 150

Bacterial RNAs, 129

Bacteriorhodopsin, 232

BALB genotype, 365–366

Barth syndrome, 280, 317

Bax family, 394–396

Bax-induced cytochrome c, 276

complex, 202–210, 276

Bcl-2 proteins, 389, 390, 392

anti-apoptotic, 394, 396–397

b cytochromes, 175, 198, 203, 204. See

also Cytochrome b2

Bernard, C., 170, 171

β-aminolevulinic acid (ALA), 310. See

also ALA synthase

β-amyloid precursor protein (APP), 386

effect on mitochondrial functions, 387

“Anatomically modern human,” 423

“Anchor” duplexes, 118

Anchor proteins, 151, 196, 197, 198

Animal mitochondria, factors puriﬁ ed

and characterized from, 134–135

Animal mtDNAs, 96

Antibiotics, to obtain resistant cell

lines, 353

Antimycin A, 207

ANT inhibitors, 339. See also Adenine

nucleotide transporter (ANT)

Antioxidant defense mechanisms, 274

Antiporters, 336

Apes, mtDNA sequences of, 426–428

Apo-cytochrome b gene, 14

Apoptosis, 11

cell progression toward, 242

mitochondria and, 389–398

mitochondrial alterations in, 55

role of oxygen species in, 274

ROS production and, 276

stages of, 391

stimuli for, 391

VDAC and, 331

Apoptosis inducing factor (AIF), 393

“Apoptosome,” 394

Arabidopsis thaliana, mitochondrial

genome of, 70–71

Archaebacteria, 12–13

ARg2 rule, 143

Ascaris suum, 199

Assembly factors, 258

late-stage, 204

a subunits, 255

ATM1 gene, 327

Atmungsferment, 171, 220

ATP (adenosine triphosphate), 2

concentrations of, 145

consumption of, 262

formation of, 252

hydrolysis of, 251

proton-conductance pathway by, 271

rate of consumption of, 261

synthesis of, 172–173

turnover of, 265, 266, 371

as a versatile intermediate, 228–229

atp6 gene, 401

atp9 transcript, 123

ATP/ADP antiport system, 262

INDEX 443

β-barrel proteins, 148, 330

β-oxidation reactions, 305, 307

BH domains, 396

Bid protein, 395, 397

Binuclear heme a

–Cu

center, 217

Biochemical fractionations, 179–182

Bioenergetics, 168, 184–185

Biparental inheritance, 419

Blood, role of hemoglobin in, 169

Blue-Native polyacrylamide gel

electrophoresis (BN-PAGE), 182,

192, 203

Bongkrekic acid, 333, 334

“Bottleneck,” 362, 363, 364, 365

in oxidative phosphorylation, 371

in a pathway, 260

Bovine F

subcomplex, 255

Bovine F

-ATPase, 246

Brassica napus, cytoplasmic male

sterility in, 400–402

BrdU, 103

Brown adipocyte, 267

Brown adipose tissue, 267

Brownian ratchet model, 149, 257

b subunits, 255

b-type cytochromes, 313

(calcium ion), channel formation

and, 339

concentrations, subcellular, 338.

See also Ca

entries

Cytoplasmic male sterility (CMS),

in plants, 400–404

“Cytoplasmic” mutations, 9, 84

Cytoplasmic petites, 349

Cytoplasmic protein synthesis, 13

Cytoskeleton, mitochondrial interaction

with, 34–37

Cytosol, protein turnover in, 155–156

Cytosolic aconitase, 178, 301–302

Cytosolic chaperones, 83

Cytosolic machinery, 327

Cytosolic SOD, 274–275

Cytosolic translation, factors active in,

133–134

DDP1 protein, 376–377

Deadenylation reaction, 90

Deafness, 372–373

Deafness and dystonia syndrome

(DDS), 376–377

Deaminase activity, 122

Degradation, mitochondrial, 54

Dehydrogenases, stimulation in the

Krebs cycle, 263–264

Dehydrogenations, 172

Deletions, mapping, 358–359

δ subunit, 253

Deoxynucleoside triphosphate synthesis,

103. See also ATP entries

Dicyclohexylcarbodiimide (DCCD),

inhibition of F

ATPase by,

256

Dideoxy cytidine (ddCTP), 351

Dihydrofolate reductase (DHFR), 142,

144

Dihydrolipoyl dehydrogenase, 303

Dimethylallyl-pyrophosphate (DMA-

PP), 319

Diseases, mitochondrial, 5

446 INDEX

Displacement loop (D-loop), 97, 98, 99,

107, 108

existence and persistence of, 101–102

in forensic applications, 430–431

DNA (deoxyribonucleic acid)

ancient, 424

covalent modiﬁ cations of, 382

in kinetoplasts, 76

mitochondrial, 4–5

Y chromosome, 429

DNA-binding peptide, 93

DNA circles, 76

DNA “kinks,” 79

DNA replication, 96–97

defective, 375

in mammalian mitochondria, 96–104

priming and initiation of, 98

DNA–RNA metabolism, transcription

of, 105–125

Dnm1p protein, 41

Drosophila

as an experimental genetic system, 55

mutants of, 51–52

Drug-induced parkinsonism, 384

Dyes, use in investigating mitochondria,

240

Ecstacy, 269–270

Editing, approach to identifying, 122

Editing sites, 122

EF-Tu factor, 136

EF-Tu

activity, 135

eIF translation factors, 133, 134

Electrochemical fuel cells, 231

Electroneutrality principle, 239

Electron leakage, 275

Electron microscopy, 3, 18, 19, 20

Electron paramagnetic resonance

(EPR), 177

Electron pathway, cyanide-insensitive,

225–226

Electron spin resonance (ESR), 177

Electron transport, 224–228

proton pumping and, 211–212, 214

Electron transport chain, 123, 172, 173–

224, 180–182

biochemical components of, 173–179

contributions to deﬁ ning, 176–177

defective, 373–375

“solid-state” model for, 183

Electron transport chain complexes, xii

assembly of, 220–224

separation of, 179–184

Electron transport inhibitors, 206–207

“Elementary particle,” 4

Embden–Meyerhof pathway, 228

Endonucleolytic cleavages, 114

Endoplasmic reticulum (ER), 31

Endothelial NOS, 277

Energy charge, 262

Energy demands, regulatory

mechanisms for, 259

Energy metabolism

defects in, 346

huntingtin and, 388–389

in trypanosomes, 227–228

“Energy-rich” compounds, 172

Enzyme cascade model, 118

Enzymes

ﬂ ux sensitivity to, 260

for maintenance/expression of

mitochondrial genome, 82–85

Enzymology, 172

ε subunit, 253

“Error catastrophe” hypothesis, 276,

380

Error-prone DNA polymerase γ model,

276

ERV1 gene, 327

Escherichia coli

proliferation of, 199

23S rRNA in, 130

ESSS subunit, 192, 222

Eubacteria, 12–13

Eukaryotes, 12–13

fumarate reduction in, 199–200

translation factors in, 133, 134

Eukaryotic cells, 9

evolution of, 8

Eukaryotic complexes, 186

Evolution

of eukaryotic cells, 8

human, 419–426

primate, 426–428

Excision repair, 104

Expressivity, 362

complex, 245

subcomplex, 244, 245, 249

proton ﬂ ow and, 253–257

INDEX 447

-ATPase, 244–246. See also

F-ATPases

rotary motion of, 250

subcomplex fractionation, 250

-ATP synthase, 4. See also F

-ATPase

complex, subunit stoichiometry of,

250

subcomplex

with ATPase activity, 258

X-ray structure of, 247–249

FAD (ﬂ avin adenine dinucleotide), 305

Familial mitochondrial DNA depletion,

369

Farnesyl-pyrophosphate (FPP), 319,

321–322

Fasciola hepatica, 324

Fast dyes, 242–243

F-ATPases, 251. See also F

-ATPase

entries

Fatty acids

in cardiolipin, 280

degradation of, 305

metabolism of, 304–308

transport of, 271

Fenton reaction, 273

Fe–S clusters. See also Iron–sulfur

clusters

in bacteria, 325

biogenesis of, 328

formation of, 327

in proteins, 325

“Fe–S lock,” 239

Fe–S protein

biogenesis of, 325, 328

maturation of, 328

15-kDa peptide, 402–403

Filament formation, 47

Fis1p-Mdv1p protein, 41

Fis1p protein, 41

Fission, mitochondrial proliferation and,

40–41

5′UTRs, 132–133, 137

cis-acting sequences in, 138

Flagellar motor, 250–251

Flanking genes, 107–108

Flavin mononucleotide (FMN), 175–176

Flavoproteins, 175, 177

Flippase, 317

model, 268

“Flow diversion hypothesis,” 320–321

“Fluid mosaic model,” 29

Fluorescence microscopy, 30–31

Fluorescent Ca

indicators, 338

Fluorescent dyes

probing mitochondrial membrane

potential with, 239–243

properties of, 240

Flux, control of, 259–260

Flux control coefﬁ cient, 260, 266

Forensics, use of mtDNA

polymorphisms in, 432–433

Fp gene, 196

Fp–Ip complex (SDH), 197

Fp subunit, 196

Fractionations

biochemical, 179–182

of subcellular membranous structures,

318

Frataxin, 326, 376

Free energy change, 184, 231, 266

use in biological systems, 228

Free energy release, coupled to ATP

synthesis, 229

Free fatty acids, 267, 268

“Free” metal ions, 274

Free radicals, 272, 381

Friedreich’s ataxia, 376

Fruton, H. J., 172

Fruton, J. S., 170

F-type Na

-ATPase rotor ring, structure

of, 249

Fumarate reduction, 198–200

Functional deterioration hypothesis, 383

Fungi

mitochondrial genome in, 72–75

phytopathogenicity of, 81

senescence of, 80–81, 398–399

Fusion, mitochondrial, 42–46

Fusion-defective mitochondria, 38

Fusion proteins, 42, 43, 255

Futile cycles, 264

Fzo1 protein, 44

Fzo gene, 43–44

fzo mutant, 51–52

GABP transcription factor, 93

G+C clusters, 74–75

Gene disruption experiments, 201

Gene expression, regulation by carbon

source, 89–90

448 INDEX

Gene knockouts, 192

Gene linkages, 75

Genes

compact arrangement of, 106

involved in mitochondrial fusion and

ﬁ ssion, 42

in kDNA maxicircles, 78

repeat-associated, 70

mitochondrial DNA mutations and, 5

Genetic diseases, 346–348

Genetic manipulations, 221

Genome compatibility test, 95

Genomes

“interactions” between, 85

role of mitochondria in, xiv

Geranyl-geranyl-pyrophosphate

(GGPP), 321–323

GGPP synthases, 322

Glucose repression, 86, 89, 349

Glutathione (GSH), 275

Glycolysis, 173

Glycosomes, 228

Glyoxylate cycle, 300

Glyoxysomes, 305

Grandmothers of the Plaza de Mayo,

mtDNA haplotyping for, 431

Gray, M. W., 8

Green ﬂ uorescent protein (GFP), 31,

38–40

GRIM-19 gene/protein, 187

Group transfer reactions, 229, 231

Growth factor deprivation, apoptosis

and, 391

GTPases, multidomain, 52

GTP hydrolysis, 42

Guide RNA genes, 78, 79

Guide RNAs (gRNAs), 117–118

Haemonchus contortus, 199

Halobacter halobium model system,

232–233

Hap1p protein, 87, 88

Hap2/3/4 complex, 87, 88

Hap2/3/4 peptides, 88

Hateﬁ , Y., 179

puriﬁ cation scheme devised by, 180

Heat-shock proteins, Trichomonas

nuclear genes of, 14–15

Heavy-strand promoter (HSP), 9S

HeLa cells, 31, 103, 106

chloramphenicol-resistant, 352

mRNA turnover in, 124–125

HeLa mitochondria, GFP in, 39–40

Helmholtz, Hermann von, 170

Heme, substituents in, 311–313

Heme biosynthesis, 309–314

oxygen and, 313

Heme irons, distances between, 206

Heme prosthetic group, 174

Heteroplasmic mice, 353

Heteroplasmy, 363, 365, 368

HEXXH sequence, 155

High-energy phosphate bonds, 173,

229–230

High-mobility group proteins (HMG),

109

HMG-CoA reductase, 319–320, 321

Homo erectus, 423

Homology cloning, 38

“Homology cloning/cybersearching,”

135

Homo neanderthalensis, 424–425

Homoplasmic hybrid plants, 69

Homoplasmic null mutations, 367

Homoplasmy, 360–361, 362

Homo sapiens, 424. See also Human

entries

epochs in the evolution of, 423

expansion of, 422

/O ratio, 234–235. See also Proton

entries

“Hot spots,” 433

hsp70 heat-shock protein family,

146–147

H-strand promoters, 107

H-strand synthesis, 97

Human evolution, 419–426

Human genetic diseases, 346–348

Human mitochondrial diseases,

molecular genetics of, 354–377

Human mitochondrial genome, 61

Internet updates on, 64

map of, 66

Human Mitochondrial Genome

Database (mtDB), 425–426

Human mitochondrial transport

proteins, 335

Human mtDNA sequence, 65

INDEX 449

Human nuclear genome, 422

Human Y chromosome variation,

428–430

geographic distribution of, 429–430

hu-mtTFA, 109

Huntingtin (HTT), 388

Huntington’s disease (HD), 387–389

hu-POLRMT, 108

Hybrids, interspeciﬁ c, 353

Hydra attenuata, mitochondrial genome

of, 64

Hydrogenosomes, 14–15

“Hydrophilic site,” 193

Hydrophobic peptides, 14

“Hydrophobic site,” 193

Hydroxyl radical, 272–273, 276

“Hysteric” enzyme, 218

I-AAA-protease, 155

IF1 inhibitory protein, 248–249

Immunoﬂ uorescence studies, 30

Import methods, 146

Import motor, 149

Import studies, isolated mitochondria

in, 142

IMS proteins, 148, 150–151

Inducible NOS, 277

Inhibitors, complex II, 198

Initiation factors (eIFs), 90

Inner mitochondrial membrane, 29

Institute for Enzyme Research, 4

Integral membrane proteins (IMPs), 65,

143–144, 151

Intergenic sequences, (A+T)-rich, 75

Interleukin 1β converting enzyme

(ICE), 392

Intermediates, characterizing, 221

Intermembrane compartment, 26

Intracellular Ca

“sinks,” 337

Intracristal compartment, 26

“Intrinsic motility,” 34

mitochondrial, 37

“Intrinsic uncoupling,” 265

Introns, 71

disrupted, 116

mobile, 74, 79

ω genetic system and, 73–74

optional, 73

ORFs and, 115

In vitro mitochondrial fusion assay,

44–45

In vitro mitochondrial protein synthesis,

133

In vitro transcription systems, 112

Ionophores, 236

Ion pumps, 231–232

Ip peptides (SDH2), 196

eukaryotic genes for, 201

Iron-regulatory protein 1 (IRP-1), 325

Iron-responsive elements (IREs), 178,

302, 312, 325

Iron–sulfur centers, 178–179

biosynthesis of, 324–329

Iron–sulfur clusters, 177–179, 190, 196,

205. See also Fe–S clusters

Iron–sulfur protein (ISP), 203, 237,

239

ISC-assembly complex, 328

ISC machinery, 325–326

Isocitrate dehydrogenase, 302–303

Isopentenyl-pyrophosphate (IPP), 319

IT-15 gene, 387

J-aggregate ﬂ uorescence, 243

JC-1 cyanine dye, 243

Joule, James, 169–170

Junk DNA, 15, 75

Kalilo linear plasmid, 80

kDNA, 76–78

kDNA maxicircles, 76, 78

kDNA minicircles, 76

gene content of, 78

Kearns–Sayre syndrome (KSS), 367,

368

Keilin, D., 171

Ketogenesis, 308

Ketoglutarate, 309

α-Ketoglutarate dehydrogenase, 303

antiporter, 336. See also Proton

entries

Kinases, in axonal transport of

mitochondria, 36–37

Kinetoplastid protozoa

mitochondrial genome in, 75–79

RNA editing in, 116–121

Kinetoplasts, 20, 32, 76

constant, 263

450 INDEX

Knock-out mice, Bcl-2, Bcl-x, or Bax,

397

Krebs cycle, 84–85, 173, 177, 196, 199,

299–304

Languages, comparative analysis of, 425

Lavoisier, Antoine, 169

“Leaky” phenotype, 361

Leber’s hereditary optic neuropathy

(LHON), 359–361, 369–371

Leigh syndrome, 223–224

Leishmania infantum, 200

Leishmania tarentolae, 76, 77, 121, 152,

153

Leloir pathway, 350

Lewy bodies, 385

LHON mutations, 370. See also Leber’s

hereditary optical neuropathy

(LHON)

Life-span research, 398

Light/ﬂ uorescence microscope, 19

Light-strand promoter (LSP), 98, 109

Linear mitochondrial DNAs, 63

Linear plasmids, 79

properties related to replication,

79–80

Linkage studies, 375

Lipids

biosynthesis/metabolism of, 314–318

delivery to mitochondria, 317

origin and site of synthesis of, 318

role of, 279–281

Lipophilic cationic dyes, 31

Lou Gehrig’s disease, 389

LSP transcripts, 98

L-strand promoters, 107

L-strand synthesis, 97, 101

L-strand transcripts, 107

Lysine isoacceptors, 152

Lysosomes, 299

M1P1 gene, 105

m-AAA-protease, 155

Maintenance of mitochondrial

morphology (Mmm1p) gene

product, 47

Maize mitochondria, 81

Mammalian cells, 31

mitochondrial genome of, 352

mitochondrial protein import in, 143

mtDNA replication in, 102–103

nuclear respiratory gene regulation in,

91–95

Mammalian cells in culture,

mitochondrial mutations in,

350–354

Mammalian cytochrome oxidase, 93

Mammalian mitochondria

DNA replication in, 96–104

genomes of, 64

mtDNA repair in, 104–105

recombination in, 105

transcription in, 105–110

Mammalian mitochondrial F

complex,

255

Mammalian mtDNA, phenotypes

resulting from mutations in, 132

Mammals, complex IV structure in,

219

Maranhar linear plasmid, 80

Margulis, L., 8

Mas70 protein, 396

mas mutants, 145–146

“Master” circle, 69

Maternal inheritance, 359–362, 418

versus sporadic inheritance, 355–357

Matrix protein processing peptidase

(MPP), 205

Matrix targeting sequences, 152

Matrix targeting signal, 142, 144,

150–151

Mayer, Robert, 169

Mdm1p protein, 46–47

Mdm1 protein, 37

mdm2 mutant, 49

Mdm30 F-box protein, 45

MDMA (ecstacy; 3,4-methylenedioxy-

N-methylamphetamine), 269–270

MDM genes, 47

Meiosis, 363

in yeast, 50

MELAS (myopathy, encephalopathy,

lactic acidosis, and stroke-like

symptoms), 113. See also

Mitochondrial encephalomyopathy

with lactic acidosis and stroke-like

episodes (MELAS); Myopathy and

cardiomyopathy (MIMyCa)