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Titolo:
Effect of 'binary mitochondrial heteroplasmy' on respiration and ATP synthesis: implications for mitochondrial diseases
Autore:
Korzeniewski, B; Malgat, M; Letellier, T; Mazat, JP;
Indirizzi:
Univ Bordeaux 2, INSERM EMI 9929, F-33076 Bordeaux, France Univ Bordeaux 2 Bordeaux France F-33076 I 9929, F-33076 Bordeaux, France Jagiellonian Univ, Inst Mol Biol, PL-31120 Krakow, Poland Jagiellonian Univ Krakow Poland PL-31120 l Biol, PL-31120 Krakow, Poland
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 357, anno: 2001,
parte:, 3
pagine: 835 - 842
SICI:
0264-6021(20010801)357:<835:EO'MHO>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYTOCHROME-C-OXIDASE; OXIDATIVE-PHOSPHORYLATION; MUSCLE MITOCHONDRIA; BRAIN MITOCHONDRIA; WILD-TYPE; IN-VIVO; DNA; MUTATION; MTDNA; COMPLEMENTATION;
Keywords:
metabolic control analysis; oxidative phosphorylation; threshold effect;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Korzeniewski, B Univ Bordeaux 2, INSERM EMI 9929, 146 Rue Leo Saignat, F-33076 Bordeaux, France Univ Bordeaux 2 146 Rue Leo Saignat Bordeaux France F-33076
Citazione:
B. Korzeniewski et al., "Effect of 'binary mitochondrial heteroplasmy' on respiration and ATP synthesis: implications for mitochondrial diseases", BIOCHEM J, 357, 2001, pp. 835-842

Abstract

Respiratory-chain-complex subunits in mitochondria are encoded by nuclear or mitochondrial DNA. This property might have profound implications for the phenotypic expression of mutations affecting oxidative phosphorylation complexes. The aim of this paper is to study the importance of the origin of the mutation (nuclear or mitochondrial) on the expression of mitochondrial defects. We have therefore developed theoretical models illustrating three mechanisms of nuclear or mitochondrial DNA mutation giving rise to a deficiency in the respiratory-chain complex: (1) a partial deficiency, homogeneously distributed in all of the mitochondria; (2) a complete deficiency, onlyaffecting some of the mitochondria ('binary mitochondrial heteroplasmy'); and (3) a partial deficiency, affecting only some of the mitochondria. We show that mutations affecting oxidative phosphorylation complexes will be expressed in different ways depending on their origins. Although the expression of nuclear or mitochondrial mutations is evidence of a biochemical threshold, we demonstrate that the threshold value depends on the origin and distribution of the mutation (homogeneous or not) and also on the energy demand of the tissue. This last prediction has been confirmed in an experimentalmodel using hexokinase for the simulation of the energy demand and a variation in mitochondrial concentration. We also emphasize the possible role of'binary mitochondrial heteroplasmy' in the expression of mitochondrial DNAmutations and thus the importance of the origin of the deficit (mutation) for the diagnosis or therapy of mitochondrial diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 06:01:24