Scheffler Immo E. Mitochondria

257. MacLennan , D. H. and Tzagoloff , A. ( 1968 ) Biochemistry 7 , 1603 – 1610 .

258. Tzagoloff , A. , Byington , K. H. , and MacLennan , D. H. ( 1968 ) J. Biol. Chem. 243 ,

2405 – 2412 .

259. Tzagoloff , A. , MacLennan , D. H. , and Byington , K. H. ( 1968 ) Biochemistry 7 ,

1596 – 1602 .

260. Hekman , C. , Tomich , J. M. , and Hateﬁ , Y. ( 1991 ) J. Biol. Chem. 266 , 13564 – 13571 .

261. Ogilvie , I. , Aggeler , R. , and Capaldi , R. A. ( 1997 ) J. Biol. Chem. 272 , 16652 – 16656 .

262. Racker , E. ( 1976 ) A New Look at Mechanisms in Bioenergetics , Academic Press ,

New York .

263. Abrahams , J. P. , Leslie , A. G. W. , Lutter , R. , and Walker , J. E. ( 1994 ) Nature 370 ,

621 – 628 .

264. Leslie , A. G. W. and Walker , J. E. ( 2000 ) Philos. Trans. R. Soc. Lond. B Biol. Sci.

355 , 465 – 471 .

265. Weber , J. and Senior , A. E. ( 1997 ) Biochim. Biophys. Acta 1319 , 19 – 58 .

266. Capaldi , R. A. , Aggeler , R. ,

Turina , P. , and Wilkens

, S. ( 1994 ) Trends in Biochem. Sci.

19 , 284 – 289 .

267. Gledhill , J. R. and Walker , J. E. ( 2006 ) Biochem. Soc. Trans. 34 , 989 – 992 .

268. Gledhill , J. R. and Walker , J. E. ( 2005 ) Biochem. J. 386 , 591 – 598 .

269. Cabezon , E. , Runswick , M. J. , Leslie , A. G. , and Walker , J. E. ( 2001 ) EMBO J. 20 ,

6990 – 6996 .

270. Cabezon , E. , Montgomery , M. G. , Leslie , A. G. , and Walker , J. E. ( 2003 ) Nat. Struct.

Biol. 10 , 744 – 750 .

271. Dickson , V. K. , Silvester , J. A. , Fearnley , I. M. , Leslie , A. G. , and Walker , J. E. ( 2006 )

EMBO J. 25 , 2911 – 2918 .

272. Silvester , J. A. , Dickson , V. K. , Runswick , M. J. , Leslie , A. G. , and Walker , J. E. ( 2006 )

Acta Crystallograph. Sect. F Struct. Biol. Cryst. Commun. 62 , 530 – 533 .

273. Walker , J. E. and Dickson , V. K. ( 2006 ) Biochim. Biophys. Acta 1757 , 286 – 296 .

274. Rubinstein , J. L. , Walker , J. E. , and

Henderson , R. ( 2003 ) EMBO J. 22 , 6182 – 6192 .

275.

Meier , T. , Polzer , P. , Diederichs , K. , Welte , W. , and Dimroth , P. ( 2005 ) Science 308 ,

659 – 662 .

276. Murata , T. , Yamato , I. , Kakinuma , Y. , Leslie , A. G. W. , and Walker , J. E. ( 2005 ) Science

308 , 654 – 659 .

277. Fillingame , R. H. , Jones , P. C. , Jiang , W. , Valiyaveetil , F. I. , and Dmitriev , O. Y. ( 1998 )

Biochim. Biophys. Acta 1365 ( 1 – 2 ), 135 – 142 .

278. Boyer , P. D. ( 1993 ) Biochim. Biophys. Acta 1140 , 215 – 250 .

279. Pedersen , P. L. and Amzel , L. M. ( 1993 ) J. Biol. Chem. 268 , 9937 – 9940 .

280. Junge , W. , Lill , H. , and Engelbrecht , S. ( 1997 ) TIBS 22 , 420 – 423 .

281. Senior , A. E. , Nadanaciva , S. , and Weber , J. ( 2002 ) Biochem. Biophys. Acta 1553 ,

188 – 211 .

282. Weber , J. and Senior , A. E. ( 2003 ) FEBS Lett. 545

, 61 – 70 .

283. Senior , A. E. and Weber , J. ( 2004 ) Nature Struct. Mol. Biol. 11 , 110 – 112 .

284. Gresser , M. J. , Meyers , J. A. , and Boyer , P. D. ( 1982 ) J. Biol. Chem. 257 ,

12030 – 12038 .

REFERENCES 291

292 MITOCHONDRIAL ELECTRON TRANSFER

285. Repke , K. R. H. and Schon , R. ( 1974 ) Acta Biol. Med. Ger. 33 , K27 – K38 .

286. Adolfsen , R. and Moudrianakis , E. N. ( 1976 ) Arch. Biochem. Biophys. 172 ,

425 – 433 .

287. Yasuda , R. , Yoshida , M. , and Kinosita , K. , Jr., Noji , H. ( 1997 ) Nature 386 , 299 –

302 .

288. Yasuda , R. , Noji , H. , Yoshida , M. , Kinosita , K. , Jr. , and Itoh , H. ( 2001 ) Nature 410 ,

898 – 904 .

289. Ueno , S. , Suzuki , T. , Kinosita , K. , Jr. , and Yoshida , M. ( 2005 ) Proc. Natl. Acad. Sci.

USA 102 , 1333 – 1338 .

290. Diez , M. , Zimmermann , B. , Borsch , M. , Konig , M. , Schweinberger , E. , Steigmiller , S. ,

Reuter , R. , Felekyan , S. , Kudryatsev , V. , Seidel , C. A. M. , and Graber , P. ( 2004 ) Nature

Struct. Mol. Biol. 11 , 135 – 141 .

291. Nishizaka , T. , Oiwa , K. , Noji , H. , Kimura , S. , Muneyuki

, E. , Yoshida , M. , and Kinosita ,

K. , Jr. ( 2004 ) Nature Struct. Mol. Biol. 11 , 142 – 148 .

292. Sambongi , Y. , Iko , Y. , Tanabe , M. , Omote , H. , Iwamoto - Kihara , A. , Ueda , I. , Yanagida ,

T. , Wada , Y. , and Futai , M. ( 1999 ) Science 286 , 1722 – 1724 .

293. Nishio , K. , Iwamoto - Kihara , A. , Yamamoto , A. , Wada , Y. , and Futai , M. ( 2002 ) Proc.

Natl. Acad. Sci. USA 99 , 13448 – 13452 .

294. Boyer , P. D. ( 1997 ) Annu. Rev. Biochem. 66 , 717 – 749 .

295. Matsui , T. , Muneyuki , E. , Honda , M. , Allison , W. S. , Dou , C. , and Yoshida , M. ( 1997 )

J. Biol. Chem. 272 , 8215 – 8221 .

296. Walker , J. E. , Collinson , I. R. , Van Raaij , M. J. , and Runswick , M. J. ( 1995 ) Methods

Enzymol. 260 , 163 – 190 .

297. Law , R. H. P. , Manon , S. , Devenish , R. J. , and Nagley , P. ( 1995 ) Methods Enzymol.

260 , 133 – 163 .

298.

Fillingame , R. H. ( 1992 ) J. Bioenerg. Biomembr. 24 , 485 – 491 .

299. Junge , W. and Nelson , N. ( 2005 ) Science 308 , 642 – 644 .

300. Oster , G. and Wang , H. ( 2003 ) Trends Cell Biol. 13 , 114 – 121 .

301. Paumard , P. , Vaillier , J. , Coulary , B. , Schaeffer , J. , Soubannier , V. , Mueller ,

D. M. , Brethes , D. , Di Rago , J. - P. , and Velours , J. ( 2002 ) EMBO J. 21 , 221 –

230 .

302. Arselin , G. , Giraud , M. F. , Dautant , A. , Vaillier , J. , Brethes , D. , Coulary - Salin , B. ,

Schaeffer , J. , and Velours , J. ( 2003 ) Eur. J. Biochem. 270 , 1875 – 1884 .

303. Brown , G. C. ( 1992 ) Biochem. J. 284 , 1 – 13 .

304. Kacser , H. and Burns , J. A. ( 1997 ) Biochem. Soc. Trans. 23 , 341 – 365 .

305. Heinrich , R. and Rapoport , T. A. ( 1974 ) Eur. J. Biochem. 42 , 89 – 95 .

306. Brand , M. D. and Kesseler , A. ( 1995 ) Biochem. Soc. Trans.

23 , 371 – 376 .

307. Brand , M. D. , Chien , L. - F. , and Rolfe , D. F. S. ( 1993 ) Biochem. Soc. Trans. 21 ,

757 – 762 .

308. Papin , J. A. , Price , N. D. , Wiback , S. J. , Fell , D. A. , and Palsson , B. O. ( 2003 ) Trends

Biochem. Sci. 28 , 250 – 258 .

309. Gnaiger E. and Kuznetsov , A. V. ( 2002 ) Biochem. Soc. Trans. 30 , 252 – 258 .

310. Jin , Q. and Bethke , C. M. ( 2002 ) Biophys. J. 83 , 1797 – 808 .

311. Korzeniewski , B. ( 2002 ) Mol. Biol. Rep. 29 , 197 – 202 .

312. Kudin , A. , Vielhaber , S. , Elger , C. E. , and Kunz , W. S. ( 2002 ) Mol. Biol. Rep. 29 ,

89 – 92 .

313. Atkinson , D. E. ( 1977 ) Cellular Energy Metabolism and Its Regulation , Academic

Press , New York .

314. Klingenberg , M. ( 1961 ) Biochem. Z. 335 , 231 – 272 .

315. Erecinska , M. and Wilson , D. F. ( 1982 ) J. Membr. Biol. 70 , 1 – 14 .

316. Crompton , M. ( 1985 ) Curr. Top. Membr. Transp. 25 , 231 – 276 .

317. McCormack , J. G. , Halestrap , A. P. , and Denton , R. M. ( 1990 ) Physiol. Rev. 70 ,

391 – 425 .

318. Anthony , G. , Reimann , A. , and Kadenbach , B. ( 1993 ) Proc. Natl. Acad. Sci. USA 90 ,

1652 – 1656 .

319. Arnold , S. and Kadenbach , B. ( 1999 ) FEBS Lett. 443 , 105 – 108 .

320. Ludwig , B. , Bender , E. , Arnold , S. , Huttemann , M. , Lee , I. , and Kadenbach , B. ( 2001 )

Eur. J. Chem. Biol 2 , 392 – 403 .

321. Kadenbach , B. ( 2003 ) Biochim. Biophys. Acta 1604

, 77 – 94 .

322.

Linder , D. , Freund , R. , and Kadenbach , B. ( 1995 ) Comp. Biochem. Physiol. B

Biochem. Mol. Biol. 112 , 461 – 469 .

323. Rohdich , F. and Kadenbach , B. ( 1993 ) Biochemistry 32 , 8499 – 8503 .

324. Kadenbach , B. , Huettemann , M. , Arnold , S. , Lee , I. , and Bender , E. ( 2000 ) Free Radic.

Biol. Med. 29 , 211 – 221 .

325. Saccone , C. , Pesole , G. , and Kadenbach , B. ( 1991 ) Eur. J. Biochem. 195 , 151 –

156 .

326. Frank , V. and Kadenbach , B. ( 1996 ) FEBS Lett. 382 , 121 – 124 .

327. Korzeniewski , B. and Mazat , J. P. ( 1996 ) Biochem. J. 319 , 143 – 148 .

328. Wiedemann , F. R. and Kunz , W. S. ( 1998 ) FEBS Lett. 422 , 33 – 35 .

329. Nicholls , D. G. and Locke , R. M. ( 1984 ) Physiol. Rev. 64 , 164 .

330. Silva , J. E. and Rabelo , R. ( 1997 ) Eur. J. Endocrinol. 136 , 251 – 264 .

331. Cannon , B. and Nedergaard , J. ( 2004 ) Physiol. Rev.

84

, 277 – 359 .

332. Nedergaard , J. and Cannon , B. ( 1992 ) The uncoupling protein thermogenin and

mitochondrial thermogenesis . In Ernster , L. , editor. Molecular Mechanisms in

Bioenergetics , Elsevier Science , London , pp. 385 – 420 .

333. Fleury , C. , Neverova , M. , Collins , S. , Raimbault , S. , Champigny , O. , Levi - Meyrueis , C. ,

Bouillaud , F. , Seldin , M. F. , Surwit , R. S. , Ricquier , D. , and Warden , C. H. ( 1997 ) Nat.

Genet. 15 , 269 – 272 .

334. Esteves , T. C. and Brand , M. D. ( 2005 ) Biochim. Biophys. Acta (BBA) — Bioener-

getics 1709 , 35 – 44 .

335. Brand , M. D. and Esteves , T. C. ( 2005 ) Cell Metab . 2 , 85 – 93 .

336. Klingenberg , M. , Winkler , E. , and Huang , S. ( 1995 ) Methods Enzymol. 260, 89 ,

369 – 389 .

337. Winkler , E. , Wachter , E. , and Klingenberg , M. ( 1997 ) Biochemistry 36 , 148 – 155 .

338. Klingenberg , M. and Echtay , K. S. ( 2001 ) Biochim. Biophys. Acta 1504 , 128 – 143 .

339. Garlid , K. D. ,

Jaburek , M. , Jezek , P. , and Varecha , M. ( 2000 ) Biochim. Biophys. Acta

1459 , 383 – 389 .

REFERENCES 293

294 MITOCHONDRIAL ELECTRON TRANSFER

340. Wohlrab , H. ( 2005 ) Biochim. Biophys. Acta 1709 , 157 – 168 .

341. Breen , E. P. , Gouin , S. G. , Murphy , A. F. , Haines , L. R. , Jackson , A. M. , Pearson , T. W. ,

Murphy , P. V. , and Porter , R. K. ( 2006 ) J. Biol. Chem. 281 , 2114 – 2119 .

342. Arechaga , I. , Raimbault , S. , Prieto , S. , Levi - Meyrueis , C. , Zaragoza , P. , Miroux , B. , Ric-

quier , D. , Bouillaud , F. , and Rial , E. ( 1993 ) Biochem J. 296 , 693 – 700 .

343. Ledesma , A. , De Lacoba , M. G. , and Rial , E. ( 2002 ) Genome Biol. 3 , reviews

3015.1 – 3015.9 .

344. Mills , E. M. , Banks , M. I. , Sprague , J. E. , and Finkel , T. ( 2003 ) Nature 426 ,

403 – 404 .

345. Esteves , T. C. and Brand , M. D. ( 2005 ) Biochim. Biophys. Acta 1709 , 35 – 44 .

346. Brookes , P. S. ( 2005 ) Free Radic. Biol. Med. 38 , 12 – 23 .

347. Prieto , S. , Bouillaud , F. , Ricquier

, D. , and

Rial , E. ( 1992 ) Eur. J. Biochem. 208 ,

487 – 491 .

348. Prieto , S. , Bouillaud , F. , and Rial , E. ( 1995 ) Biochem. J. 307 , 657 – 661 .

349. Prieto , S. , Bouillaud , F. , and Rial , E. ( 1996 ) Arch. Biochem. Biophys. 334 , 43 – 49 .

350. Laloi , M. , Klein , M. , Riesmeier , J. W. , and Muler - Rober , B. ( 1997 ) Nature 389 ,

135 – 136 .

351. Meeuse , B. J. D. ( 1975 ) Annu. Rev. Plant. Physiol. 26 , 117 – 126 .

352. Rhee , S. G. ( 2006 ) Science 312 , 1882 – 1883 .

353. Brunelle , J. K. , Bell , E. L. , Quesada , N. M. , Vercauteren , K. , Tiranti , V. , Zeviani , M. ,

Scarpulla , R. C. , and Chandel , N. S. ( 2005 ) Cell Metab. 1 , 409 – 414 .

354. Guzy , R. D. , Hoyos , B. , Robin , E. , Chen , H. , Liu , L. , Mansﬁ eld , K. D. , Simon , M. C. ,

Hammerling , U. , and Schumacker , P. T. ( 2005 )

Cell Metab. 1

, 401 – 408 .

355. Halliwell , B. and Gutteridge , J. M. ( 1999 ) Free Radicals in Biology and Medicine ,

3rd ed. , Oxford University Press , Oxford .

356. Finkel , T. ( 2003 ) Curr. Opin. Cell Biol. 15 , 247 – 254 .

357. Saltman , P. ( 1989 ) Semi. Hematol. 26 , 249 – 255 .

358. Halliwell , B. and Cross , C. E. ( 1994 ) Environ. Health Perspect. 102 , 5 – 12 .

359. Rodriguez , R. and Redman , R. ( 2005 ) Proc. Natl. Acad. Sci USA 102 , 3175 – 3176 .

360. Scandalios , J. G. ( 2002 ) Trends Biochem. Sci. 27 , 483 – 486 .

361. Jezek , P. and Hlavata , L. ( 2005 ) Int. J. Biochem. Cell Biol. 37 , 2478 – 2503 .

362. Grivennikova , V. G. and Vinogradov , A. D. ( 2006 ) Biochim. Biophys. Acta 1757 ,

553 – 561 .

363. Kussmaul , L. and Hirst , J. ( 2006 ) Proc. Natl. Acad. Sci USA 103 , 7607 – 7612 .

364. Chen , Q. , Vazquez , E. J. , Moghaddas , S. , Hoppel , C. L. , and Lesnefsky , E. J. ( 2003 )

J. Biol. Chem. 278 , 36027 – 36031 .

365. Muller , F. L. , Liu , Y. , and

Van Remmen , H. ( 2004 ) J. Biol. Chem.

279 ,

49064 – 49073 .

366. McLennan , H. R. and Degli , E. M. ( 2000 ) J. Bioenerg. Biomembr. 32 , 153 –

162 .

367. Neuzil , J. , Wang , X. F. , Dong , L. F. , Low , P. , and Ralph , S. J. ( 2006 ) FEBS Lett. 580 ,

5125 – 5129 .

368. Genova , M. L. , Pich , M. M. , Bernacchia , A. , Bianchi , C. , Biondi , A. , Bovina , C. , Falasca ,

A. I. , Formiggini , G. , Castelli , G. P. , and Lenaz , G. ( 2004 ) Ann. NY Acad. Sci. 1011 ,

86 – 100 .

369. Adam - Vizi , V. and Chinopoulos , C. ( 2006 ) Trends Pharmacol. Sci. 27 , 639 – 645 .

370. Galkin , A. and Brandt , U. ( 2005 ) J. Biol. Chem. 280 , 30129 – 30135 .

371. McCord , J. M. and Fridovich , I. ( 1969 ) J. Biol. Chem. 244 , 6059 – 6055 .

372. Bacman , S. R. , Bradley , W. G. , and Moraes , C. T. ( 2006 ) Mol. Neurobiol. 33 ,

113 – 131 .

373. Ferri , A. , Cozzolino , M. , Crosio , C. , Nencini , M. , Casciati , A. , Butler Gralla , E. , Rotilio ,

G. , Selverstone Valentine , J. , and Carri , M. T. ( 2006 ) Proc. Natl. Acad. Sci. USA 103 ,

13860 – 13865 .

374. Manfredi , G. and Xu , Z. ( 2005 ) Mitochondrion 5 , 77 – 87 .

375.

Dawson , V. L. ( 2004 ) Nat. Med. 10 , 905 – 906 .

376. Sun , J. and Trumpower , B. L. ( 2003 ) Arch. Biochem. Biophys. 419 , 198 – 206 .

377. Kirkland , R. A. and Franklin , J. L. (2006) Exp. Neurol . 204 , 458 – 461 .

378. Trifunovic , A. , Wredenberg , A. , Falkenberg , M. , Spelbrink , J. N. , Rovio , A. T. , Bruder ,

C. E. , Bohlooly , Y. , Gidlof , S. , Oldfors , A. , Wibom , R. , Tornell , J. , Jacobs , H. T. , and

Larsson , N. G. ( 2004 ) Nature 429 , 417 – 423 .

379. Trifunovic , A. , Hansson , A. , Wredenberg , A. , Rovio , A. T. , Dufour , E. , Khvorostov , I. ,

Spelbrink , J. N. , Wibom , R. , Jacobs , H. T. , and Larsson , N. G. ( 2005 ) Proc. Natl. Acad.

Sci. USA 102 , 17993 – 17998 .

380. Kujoth , G. C. , Hiona , A. , Pugh , T. D. , Someya , S. , Panzer , K. , Wohlgemuth , S. E. , Hofer ,

T. , Seo , A. Y. , Sullivan , R. , Jobling

, W. A. , Morrow

, J. D. , Van Remmen , H. , Sedivy , J.

M. , Yamasoba , T. , Tanokura , M. , Weindruch , R. , Leeuwenburgh , C. , and Prolla , T. A.

( 2005 ) Science 309 , 481 – 484 .

381. Murphy , M. P. ( 2006 ) Am. J. Physiol. Heart Circ. Physiol. 290 , H1754 – H1755 .

382. Ross , M. F. , Da Ros , T. , Blaikie , F. H. , Prime , T. A. , Porteous , C. M. , Severina , I. I. ,

Skulachev , V. P. , Kjaergaard , H. G. , Smith , R. A. , and Murphy , M. P. ( 2006 ) Biochem.

J. 400 , 199 – 208 .

383. James , A. M. , Cocheme , H. M. , and Murphy , M. P. ( 2005 ) Mech. Ageing Dev. 126 ,

982 – 986 .

384. Reddy , P. H. ( 2006 ) J. Biomed. Biotechnol. 2006 , 31372 .

385. Brookes , P. S. ( 2004 ) Mitochondrion 3 , 187 – 204 .

386. Haynes , V. , Elfering , S. , Traaseth , N. , and Giulivi , C. ( 2004 ) J Bioenerg. Biomembr.

36 , 341 – 346 .

387. Valdez , L. B. , Zaobornyj

, T. , and Boveris , A. ( 2006 ) Biochim. Biophys. Acta

1757 ,

166 – 172 .

388. Giulivi , C. , Kato , K. , and Cooper , C. E. ( 2006 ) Am. J Physiol Cell Physiol 291 ,

C1225 – C1231 .

389. Guo , F. Q. and Crawford , N. M. ( 2005 ) Plant Cell 17 , 3436 – 3450 .

390. Clementi , E. and Nisoli , E. ( 2005 ) Comp. Biochem. Physiol. A Mol. Integr. Physiol.

142 , 102 – 110 .

391. Brown , G. C. ( 2001 ) Biochim. Biophys. Acta 1504 , 46 – 57 .

REFERENCES 295

296 MITOCHONDRIAL ELECTRON TRANSFER

392. Lahiri , S. , Roy , A. , Baby , S. M. , Hoshi , T. , Semenza , G. L. , and Prabhakar , N. R. ( 2005 )

Prog. Biophys. Mol. Biol. 91 , 249 – 286 .

393. Antunes , F. , Boveris , A. , and Cadenas , E. ( 2004 ) Proc. Natl. Acad. Sci. USA 101 ,

16774 – 16779 .

394. Mason , M. G. , Nicholls , P. , Wilson , M. T. , and Cooper , C. E. ( 2006 ) Proc. Natl. Acad.

Sci. USA 103 , 708 – 713 .

395. Castello , P. R. , David , P. S. , McClure , T. , Crook , Z. , and Poyton , R. O. ( 2006 ) Cell

Metab 3 , 277 – 287 .

396. Burwell , L. S. , Nadtochiy , S. M. , Tompkins , A. J. , Young , S. M. , and Brookes , P. S. ( 2005 )

Biochem. J. 394 , 627 – 634 .

397. Hurd , T. R. , Costa , N. J. , Dahm , C. C. , Beer , S. M. , Brown , S. E. , Filipovska , A. , and

Murphy , M. P. ( 2005 ) Antioxid. Redox. Signal. 7 , 999 – 1010 .

398. Hurd , T. R. , Filipovska , A. ,

Costa , N. J. , Dahm

, C. C. , and Murphy , M. P. ( 2005 )

Biochem. Soc. Trans. 33 , 1390 – 1393 .

399. Beer , S. M. , Taylor , E. R. , Brown , S. E. , Dahm , C. C. , Costa , N. J. , Runswick , M. J. , and

Murphy , M. P. ( 2004 ) J. Biol. Chem. 279 , 47939 – 47951 .

400. Nisoli , E. , Clementi , E. , Paolucci , C. , Cozzi , V. , Tonello , C. , Sciorati , C. , Bracale , R. ,

Valerio , A. , Francolini , M. , Moncada , S. , and Carruba , M. O. ( 2003 ) Science 299 ,

896 – 899 .

401. Scarpulla , R. C. ( 2002 ) Biochim. Biophys. Acta 1576 , 1 – 14 .

402. Scarpulla , R. C. ( 2002 ) Gene 286 , 81 – 89 .

403. Scarpulla , R. C. ( 2006 ) J. Cell. Biochem. 97 , 673 – 683 .

404. Nisoli , E. , Tonello , C. , Cardile , A. , Cozzi , V. , Bracale , R. , Tedesco , L. , Falcone , S. ,

Valerio , A. , Cantoni , O. ,

Clementi , E. , Moncada , S. , and Carruba , M. O. ( 2005 ) Science

310 , 314 – 317 .

405. Robinson , N. C. , Zborowski , J. , and Talbert , L. H. ( 1990 ) Biochemistry 29 ,

8962 – 8969 .

406. Yue , W. H. , Zou , Y. P. , Yu , L. , and Yu , C. A. ( 1991 ) Biochemistry 30 , 2303 – 2306 .

407. Eble , K. S. , Coleman , W. B. , Hantgan , R. R. , and Cunningham , C. C. ( 1990 ) J. Biol.

Chem. 265 , 19434 – 19440 .

408. Beyer , K. and Klingenberg , M. ( 1985 ) Biochemistry 24 , 3821 – 3826 .

409. Schlame , M. and Haldar , D. ( 1993 ) J. Biol. Chem. 268 , 74 – 79 .

410. Schlame , M. , Brody , S. , and Hostetler , K. Y. ( 1993 ) Eur. J. Biochem. 212 , 727 – 735 .

411. Ohtsuka , T. , Nishijima , M. , and Akamatsu , Y. ( 1993 ) J. Biol. Chem. 268 ,

22908 – 22913 .

412. Ohtsuka , T. , Nishijima , M. , Suzuki , K. , and Akamatsu , Y. ( 1993 ) J. Biol. Chem.

268 ,

22914 – 22919 .

413. Schlame , M. , Rua , D. , and

Greenberg , M. L. ( 2000 ) Prog. Lipid Res. 39 , 257 – 288 .

414. Gohil , V. M. , Hayes , P. , Matsuyama , S. , Schagger , H. , Schlame , M. , and Greenberg , M.

L. ( 2004 ) J. Biol. Chem. 279 , 42612 – 42618 .

415. Li , G. , Chen , S. , Thompson , M. N. , and Greenberg , M. L. ( 2006 ) Biochim. Biophys.

Acta 1771 , 432 – 441 .

416. McKenzie , M. , Lazarou , M. , Thorburn , D. R. , and Ryan , M. T. ( 2006 ) J. Mol. Biol. 361 ,

462 – 469 .

417. Iverson , S. L. and Orrenius , S. ( 2004 ) Arch Biochem Biophys. 423 , 37 – 46 .

418. Domenech , O. , Sanz , F. , Montero , M. T. , and Hernandez - Borrell , J. ( 2006 ) Biochim.

Biophys. Acta 1758 , 213 – 221 .

419. Choi , S. Y. , Gonzalvez , F. , Jenkins , G. M. , Slomianny , C. , Chretien , D. , Arnoult , D. ,

Petit , P. X. , and Frohman , M. A. (2006) Cell Death Differ . 14 , 597 – 606 .

420. Schlame , M. , Ren , M. , Xu , Y. , Greenberg , M. L. , and Haller , I. ( 2005 ) Chem. Phys.

Lipids 138 , 38 – 49 .

421. Barth , P. G. , Valianpour , F. , Bowen , V. M. , Lam , J. , Duran , M. , Vaz , F. M. , and Wanders ,

R. J. ( 2004 ) Am. J. Med. Genet. A 126 , 349 – 354 .

422. Brandner , K. , Mick , D. U. , Frazier , A. E. , Taylor , R. D. , Meisinger , C. , and Rehling , P.

( 2005 ) Mol. Biol. Cell 16 , 5202 – 5214 .

423. Hauff , K. D. and Hatch , G. M. ( 2006 ) Prog. Lipid Res. 45 , 91 – 101 .

424. Xu , Y. , Malhotra , A. , Ren , M. , and Schlame , M. ( 2006 ) J. Biol. Chem. 281

,

39217 – 39224 .

425. Xu , Y. , Condell , M. , Plesken , H. , Edelman - Novemsky , I. , Ma , J. , Ren , M. , and Schlame ,

M. ( 2006 ) Proc. Natl. Acad. Sci. USA 103 , 11584 – 11588 .

426. Palsdottir , H. and Hunte , C. ( 2004 ) Biochim. Biophys. Acta (BBA) — Biomembr.

1666 , 2 – 18 .

REFERENCES

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6

Mitochondria, Second Edition, by Immo E. Schefﬂ er

METABOLIC PATHWAYS

INSIDE MITOCHONDRIA

Summary

Many reactions taking place inside of mitochondria occupy a central position on any

metabolic chart. The subject is well covered in most standard biochemistry textbooks

and is undoubtedly a very familiar subject to many readers. Biochemical pathways

are taken for granted, and little time is devoted nowadays to the painstaking analy-

tical studies that were necessary to establish the reaction sequences and the various

intermediates and branch points. It is not the intention to make up for this deﬁ ciency

here. However, the present treatment of mitochondria would be incomplete without

reference to the major biochemical pathways, and to the variety of enzymes localized

in the matrix or the inner mitochondrial membrane. Fatty acid oxidation and the

Krebs cycle (tricarboxylic acid cycle) were in many ways the deﬁ ning reactions for

mitochondria. Other major pathways or cycles include the urea cycle, heme biosyn-

thesis, part of the reactions leading to steroid, dolichol and ubiquinone biosynthesis,

and the synthesis of a speciﬁ c lipid, cardiolipin, which is found almost exclusively in

mitochondrial membranes. A relatively recent insight is that all iron – sulfur centers

(Fe – S clusters) originate in mitochondria.

In almost all cases (Fe – S clusters being the exception) the pathways were estab-

lished some time ago. Attention is now on regulatory phenomena, on detailed struc-

tural analyses of the many different enzymes involved, and on the cloning of the

corresponding cDNAs and genes to be used in diagnostic tests in the diagnosis of

inborn errors of metabolism.

6.1 INTRODUCTION

Until about the middle of the twentieth century, investigators preparing crude

extracts from muscle and liver homogenates for the purpose of biochemical

and enzymatic studies did not pay any attention to subcellular compartmen-

talization and its potential signiﬁ cance. Thus, when Claude and Deduve at the

Rockefeller Institute perfected techniques for isolating relatively pure mito-

chondria, a new era in biochemistry began. In a short time span the enzymes

for several important metabolic pathways were localized within the mitochon-

dria, starting with the pioneering work of Lehninger and Kennedy on fatty

acid oxidation. The citric acid cycle (TCA cycle) had already been postulated

by Krebs in 1937, building on earlier work by Szent Gyorgyi and others, but

again, Lehninger and Kennedy, taking advantage of having pure, isolated

mitochondria, demonstrated in 1948 that the entire citric acid cycle takes place

inside the mitochondria. Together with the spectroscopic identiﬁ cation of cyto-

chromes in mitochondria, these discoveries led to the recognition of mitochon-

dria as the “ powerhouse of the cell. ” Mitochondria became the ﬁ rst subcellular

organelles outside of the nucleus to be functionally characterized. It took not

much longer to identify lysosomes as the organelles containing hydrolytic

enzymes, although the role of lysosomes in the overall economy of cells did

not become apparent until later. Peroxisomes were also characterized by the

discovery of a few key enzymes such as catalase, but the description of their

full complement of enzymes took several decades. Finally, the endoplasmic

reticulum (ER) and Golgi apparatus were placed ﬁ rmly in the secretory

pathway by the classical pulse - chase experiments of Jamieson and Palade and

the pioneering biochemical studies of Sabatini and Blobel. The detailed bio-

chemical and functional descriptions of the ER and Golgi constitute highlights

of the past two decades.

6.2 THE KREBS CYCLE

A description of the citric acid cycle is found in all elementary and advanced

textbooks, and its formulation ranks among the major achievements in the

study of metabolism. It was the second cycle to be postulated by Krebs, since

he had also discovered the urea cycle a few years earlier. When it was ﬁ rst

proposed by Krebs in 1937, there were still some major areas of uncertainty,

especially in the production of citrate, which Krebs formulated as the following

reaction:

pyruvate oxaloacetate citrate CO

2

+→+

It was not until coenzyme A had been discovered by Kaplan and Lipmann in

1945 that Ochoa and Lynen were able to show in 1951 that acetyl - CoA was

the intermediate in the reaction with oxaloacetate to form citrate.

THE KREBS CYCLE 299

300 METABOLIC PATHWAYS INSIDE MITOCHONDRIA

Today the reactions of the citric acid cycle are ﬁ rmly established, and the

cycle itself occupies a central position on any metabolic chart. When it is ﬁ rst

presented to students, it is frequently emphasized that the constituents of the

cycle act catalytically — that is, are themselves not being increased or con-

sumed. Subsequently, it becomes necessary to add to the catabolic functions

of the cycle anabolic functions as well; that is, cycle intermediates are being

drained off to form amino acids and numerous precursors for other biosyn-

thetic reactions. For example, succinyl - CoA is a precursor for heme synthesis.

At the same time, the α - keto dicarboxylic acids of the cycle can be formed

from the transamination of amino acids, and oxaloacetate can also be pro-

duced from the carboxylation of phosphoenolpyruvate in certain tissues such

as liver.

Reactions of the TCA cycle are also essential for complementing the reac-

tions of the glyoxylate cycle in plants. This cycle has been speculated to be an

evolutionary precursor for the TCA cycle, still sharing with it some reactions.

However, the signiﬁ cant aspect of the glyoxylate cycle is that a novel reaction

can take place with isocitrate as the substrate. Instead of being followed by

two decarboxylation reactions, isocitrate is split by isocitrate lyase to form

succinate and glyoxylate. Glyoxylate condenses with a second acetyl - CoA to

enter the cycle to form malate. The net result is the operation of a cycle that

converts two acetyl groups to succinate. The glyoxylate cycle takes place in

glyoxysomes, which are distinct organelles of plants related to peroxisomes

and found prominently in germinating seedlings. It permits the utilization of

fats and oils stored in the seeds to make carbohydrates before plant growth

and development has formed green leaves for photosynthesis. The succinate

produced has to leave the glyoxisomes and enter mitochondria, where it is

converted to oxaloacetate that can be withdrawn to form phosphoenolpyru-

vate for gluconeogenesis.

Is there anything left to discover about the citric acid cycle? All the enzymes

have been puriﬁ ed from various organisms, and many of the corresponding

genes have been or are being cloned. Catalytic mechanisms have been deﬁ ned

in considerable detail, and crystal structures of many enzymes are available.

All but one enzyme of the citric acid cycle are soluble enzymes in the mito-

chondrial matrix. The exception is succinate dehydrogenase (see Chapter 5 ),

which is part of complex II and forms the peripheral membrane component

of this complex. Its characteristics as an electron transfer complex have been

discussed elsewhere in this volume. Structure – function analyses of this complex

are now greatly enhanced by the completion of the crystal structure. Under-

standing the assembly of the complex from precursors made in the cytosol and

imported into mitochondria, the addition of Fe – S clusters to one subunit, FAD

to another, and a b - type heme to the integral membrane subunits continue to

pose questions.

For the theoretically inclined, the regulation of the ﬂ uxes of metabolites

through the cycle presents a second challenge, especially in light of (a) new

insights about the “ robustness ” of metabolic pathways and (b) the emphasis

Scheffler Immo E. Mitochondria

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