Difference between revisions of "Kunz 2000 J Biol Chem"

Latest revision as of 17:23, 16 January 2021

Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275:27741-5.

» PMID: 10869362 Open Access

Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) J Biol Chem

Abstract: In the present work, by titrating cytochrome c oxidase (COX) with the specific inhibitor KCN, the flux control coefficient and the metabolic reserve capacity of COX have been determined in human saponin-permeabilized muscle fibers. In the presence of the substrates glutamate and malate, a 2.3 6 0.2-fold excess capacity of COX was observed in ADP-stimulated human skeletal muscle fibers. This value was found to be dependent on the mitochondrial substrate supply. In the combined presence of glutamate, malate, and succinate, which supported an approximately 1.4-fold higher rate of respiration, only a 1.4 6 0.2-fold excess capacity of COX was determined. In agreement with these findings, the flux control of COX increased, in the presence of the three substrates, from 0.27 6 0.03 to 0.36 6 0.08. These results indicate a tight in vivo control of respiration by COX in human skeletal muscle. This tight control may have significant implications for mitochondrial myopathies. In support of this conclusion, the analysis of skeletal muscle fibers from two patients with chronic progressive external ophthalmoplegia, which carried deletions in 11 and 49 % of their mitochondrial DNA, revealed a substantially lowered reserve capacity and increased flux control coefficient of COX, indicating severe rate limitations of oxidative phosphorylation by this enzyme.

Cited by

Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5^th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002

Labels:

Organism: Human Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue, Enzyme Enzyme: Complex IV;cytochrome c oxidase

Coupling state: OXPHOS

HRR: Oxygraph-2k

BEC 2020.2

@@ Line 1: / Line 1: @@
 {{Publication
-|title=Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275: 27741-27745.
+|title=Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275:27741-5.
 |info=[http://www.ncbi.nlm.nih.gov/pubmed/10869362 PMID: 10869362 Open Access]
 |authors=Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G
 |year=2000
 |journal=J Biol Chem
-|abstract=In the present work, by titrating cytochrome c oxidase
+|abstract=In the present work, by titrating cytochrome c oxidase (COX) with the specific inhibitor KCN, the flux control coefficient and the metabolic reserve capacity of COX have been determined in human saponin-permeabilized muscle fibers. In the presence of the substrates glutamate and malate, a 2.3 6 0.2-fold excess capacity of COX was observed in ADP-stimulated human skeletal muscle fibers. This value was found to be dependent on the mitochondrial substrate supply. In the combined presence of glutamate, malate, and succinate, which supported an approximately 1.4-fold higher rate of respiration, only a 1.4 6 0.2-fold excess capacity of COX was determined. In agreement with these findings, the flux control of COX increased, in the presence of the three substrates, from 0.27 6 0.03 to 0.36 6 0.08. These results indicate a tight ''in vivo'' control of respiration by COX in human skeletal muscle. This tight control may have significant implications for mitochondrial myopathies. In support of this conclusion, the analysis of skeletal muscle fibers from two patients with chronic progressive external ophthalmoplegia, which carried deletions in 11 and 49 % of their mitochondrial DNA, revealed a substantially lowered reserve capacity and increased flux control coefficient of COX, indicating severe rate limitations of oxidative phosphorylation by this enzyme.
-(COX) with the specific inhibitor KCN, the flux control
-coefficient and the metabolic reserve capacity of COX
-have been determined in human saponin-permeabilized
-muscle fibers. In the presence of the substrates glutamate
-and malate, a 2.3 6 0.2-fold excess capacity of COX
-was observed in ADP-stimulated human skeletal muscle
-fibers. This value was found to be dependent on the
-mitochondrial substrate supply. In the combined presence
-of glutamate, malate, and succinate, which supported
-an approximately 1.4-fold higher rate of respiration,
-only a 1.4 6 0.2-fold excess capacity of COX was
-determined. In agreement with these findings, the flux
-control of COX increased, in the presence of the three
-substrates, from 0.27 6 0.03 to 0.36 6 0.08. These results
-indicate a tight in vivo control of respiration by COX in
-human skeletal muscle. This tight control may have significant
-implications for mitochondrial myopathies. In
-support of this conclusion, the analysis of skeletal muscle
-fibers from two patients with chronic progressive
-external ophthalmoplegia, which carried deletions in 11
-and 49% of their mitochondrial DNA, revealed a substantially
-lowered reserve capacity and increased flux control
-coefficient of COX, indicating severe rate limitations
-of oxidative phosphorylation by this enzyme.
-|discipline=Biomedicine
 }}
+== Cited by ==
+{{Template:Cited by Gnaiger 2020 BEC MitoPathways}}
 {{Labeling
-|instruments=Oxygraph-2k
 |organism=Human
 |tissues=Skeletal muscle
 |preparations=Permeabilized tissue, Enzyme
+|enzymes=Complex IV;cytochrome c oxidase
 |couplingstates=OXPHOS
-|enzymes=Complex IV; Cytochrome c Oxidase
+|instruments=Oxygraph-2k
-|discipline=Biomedicine
+|additional=BEC 2020.2
 }}