Myocardial ischemia decreases oxidative phosphorylation through cytochrome oxidase in subsarcolemmal mitochondria

The effect of myocardial ischemia on mitochondrial oxidative phosphorylation was investigated using isolated, buffer-perfused rabbit hearts. After 45 min of global ischemia, oxidative phosphorylation was decreased only in the subsarcolemmal population of mitochondria with all substrates tested. The oxidation of N,N,N',N' tetramethyl p-phenylenediamine-ascorbate, an electron donor to cytochrome oxidase via cytochrome c, was decreased in subsarcolemmal mitochondria [ischemia (n = 6): 76 +/- 3 vs. control (n = 5): 105 +/- 6 nanoatoms O.min-1.mg-1, P < 0.01] but not in interfibrillar mitochondria. Only minor morphological changes were observed by electron microscopy in the isolated mitochondria after ischemia. Neither cytochrome oxidase activity measured under conditions for maximal activity nor the apparent Michaelis constant and maximum velocity values of the two cytochrome c binding sites were different in subsarcolemmal mitochondria isolated from ischemic and control hearts. The cytochrome c content was decreased in subsarcolemmal mitochondria after ischemia (ischemia: 0.111 +/- 0.013 vs. control: 0.156 +/- 0.007 nmol/mg protein, P < 0.05). Thus ischemia decreased the rate of oxidative phosphorylation through cytochrome oxidase selectively in intact subsarcolemmal mitochondria. Ischemic damage to the terminal segment of the electron transport chain involves a decrease in the content of cytochrome c, whereas the expressible catalytic activity of cytochrome oxidase remains unchanged.

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Myocardial ischemia selectively depletes cardiolipin in rabbit heart subsarcolemmal mitochondria

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.6.h2770 ◽

2001 ◽

Vol 280 (6) ◽

pp. H2770-H2778 ◽

Cited By ~ 121

Author(s):

Edward J. Lesnefsky ◽

Thomas J. Slabe ◽

Maria S. K. Stoll ◽

Paul E. Minkler ◽

Charles L. Hoppel

Keyword(s):

Oxidative Phosphorylation ◽

Cytochrome Oxidase ◽

Rabbit Heart ◽

Membrane Lipid ◽

Inner Mitochondrial Membrane ◽

Intact Membrane ◽

Interfibrillar Mitochondria ◽

Subsarcolemmal Mitochondria ◽

Lipid Environment ◽

Mitochondrial Membrane Lipid

Mitochondria contribute to myocyte injury during ischemia. After 30 and 45 min of ischemia in the isolated perfused rabbit heart, subsarcolemmal mitochondria (SSM), located beneath the plasma membrane, sustain a decrease in oxidative phosphorylation through cytochrome oxidase. In contrast, oxidation through cytochrome oxidase in interfibrillar mitochondria (IFM), located between the myofibrils, remains unaffected. Cytochrome oxidase activity in the intact membrane requires an inner mitochondrial membrane lipid environment enriched in cardiolipin. During ischemia, the content of cardiolipin decreased only in SSM, whereas the content of other phospholipids was preserved. Ischemia did not alter the composition of the cardiolipin that remained in SSM. Cardiolipin content was preserved in IFM during ischemia. Thus cardiolipin is a relatively early target of ischemic mitochondrial damage, leading to loss of oxidative phosphorylation through cytochrome oxidase in SSM.

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MITOCHONDRIAL BIOGENESIS DURING DIFFERENTIATION OF ARTEMIA SALINA CYSTS

The Journal of Cell Biology ◽

10.1083/jcb.58.3.643 ◽

1973 ◽

Vol 58 (3) ◽

pp. 643-649 ◽

Cited By ~ 19

Author(s):

H. Schmitt ◽

H. Grossfeld ◽

U. Z. Littauer

Keyword(s):

Cytochrome C ◽

Cytochrome Oxidase ◽

Cytochrome B ◽

Mitochondrial Biogenesis ◽

Brine Shrimp ◽

Morphological Changes ◽

Artemia Salina ◽

Mitochondrial Morphology ◽

Second Stage ◽

Two Stages

Mitochondria isolated from cysts of Artemia salina (brine shrimp) were found to be devoid of cristae and to possess a low respiratory capability. Hydration of the cysts induces marked biochemical and morphological changes in the mitochondria. Their biogenesis proceeds in two stages. The first stage is completed within 1 h and is characterized by a rapid increase in the respiratory capability of the mitochondria, their cytochrome oxidase, cytochrome b, cytochrome c and perhaps some morphological changes. In the second stage there is an increase in the protein-synthesizing capacity of the mitochondria as well as striking changes in mitochondrial morphology leading to the formation of cristae.

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Notizen: Isolation and Respiratory Assay of Earthworm Body Wall Mitochondria

Zeitschrift für Naturforschung C ◽

10.1515/znc-1984-7-829 ◽

1984 ◽

Vol 39 (7-8) ◽

pp. 853-855

Author(s):

T. V. Rao ◽

U. C. Biswal

Keyword(s):

Cytochrome C ◽

Oxidative Phosphorylation ◽

Succinate Dehydrogenase ◽

Cytochrome Oxidase ◽

Body Wall ◽

Reaction Medium ◽

Respiratory Metabolism ◽

Respiratory Enzyme ◽

Isolated Mitochondria ◽

Tissue Homogenates

Abstract Out of several media tested, KCl medium containing BSA was found to be most suitable for isolation of functionally efficient mitochondria from earthworms. Respiration and oxidative phosphorylation in isolated mitochondria are demonstrated in the presence of cytochrome c and BSA in reaction medium. Introduction - The details of the respiratory metabolism in earthworm are yet to be established. There are only a few contradictory reports on the nature of its respiratory enzyme components [1]. While, cytochrome oxidase, succinoxidase, succinate dehydrogenase were identified in earthworm tissue homogenates, the presence of Kreb′s cycle enzymes could not be demonstrated. Very little information is available on earthworm mitochondria except one report where it is isolated in 0.44 ᴍ mannitol [2]. Mitochondria from invertebrates like insects and crustaceans are isolated and characterized [3, 4]. But such methods cannot be extended to earthworms as it is known that conditions for isolation and assay of mitochondria are highly system specific [5].

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Ischemia, rather than reperfusion, inhibits respiration through cytochrome oxidase in the isolated, perfused rabbit heart: role of cardiolipin

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00348.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. H258-H267 ◽

Cited By ~ 85

Author(s):

Edward J. Lesnefsky ◽

Qun Chen ◽

Thomas J. Slabe ◽

Maria S. K. Stoll ◽

Paul E. Minkler ◽

...

Keyword(s):

Cytochrome C ◽

Cytochrome Oxidase ◽

Oxidative Capacity ◽

Rabbit Heart ◽

Early Reperfusion ◽

Perfused Rabbit Heart ◽

Transport Chain ◽

Reperfusion Period ◽

Subsarcolemmal Mitochondria ◽

Oxidative Function

Ischemia and reperfusion result in mitochondrial dysfunction, with decreases in oxidative capacity, loss of cytochrome c, and generation of reactive oxygen species. During ischemia of the isolated perfused rabbit heart, subsarcolemmal mitochondria, located beneath the plasma membrane, sustain a loss of the phospholipid cardiolipin, with decreases in oxidative metabolism through cytochrome oxidase and the loss of cytochrome c. We asked whether additional injury to the distal electron chain involving cardiolipin with loss of cytochrome c and cytochrome oxidase occurs during reperfusion. Reperfusion did not lead to additional damage in the distal electron transport chain. Oxidation through cytochrome oxidase and the content of cytochrome c did not further decrease during reperfusion. Thus injury to cardiolipin, cytochrome c, and cytochrome oxidase occurs during ischemia rather than during reperfusion. The ischemic injury leads to persistent defects in oxidative function during the early reperfusion period. The decrease in cardiolipin content accompanied by persistent decrements in the content of cytochrome c and oxidation through cytochrome oxidase is a potential mechanism of additional myocyte injury during reperfusion.

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Respiratory control and oxidative phosphorylation of the cytochrome c-cytochrome oxidase complex

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(72)90724-3 ◽

1972 ◽

Vol 47 (2) ◽

pp. 380-386 ◽

Cited By ~ 10

Author(s):

F.C. Yong ◽

Tsoo E. King

Keyword(s):

Cytochrome C ◽

Oxidative Phosphorylation ◽

Cytochrome Oxidase ◽

Respiratory Control

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Relationship between oxidative phosphorylation and adenine nucleotide translocase activity of two populations of cardiac mitochondria and mechanical recovery of ischemic hearts following reperfusion

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-114 ◽

1989 ◽

Vol 67 (7) ◽

pp. 704-709 ◽

Cited By ~ 74

Author(s):

Jianmin Duan ◽

Morris Karmazyn

Keyword(s):

Oxidative Phosphorylation ◽

Adenine Nucleotide ◽

Isolated Rat Heart ◽

Adenine Nucleotide Translocase ◽

Acute Ischemia ◽

Ventricular Contractility ◽

Interfibrillar Mitochondria ◽

Significant Depression ◽

Subsarcolemmal Mitochondria ◽

Contractile Recovery

The possible relationship of the atractyloside-sensitive adenine nucleotide translocase activity, oxidative phosphorylation, and the recovery of ventricular contractility following reperfusion of the ischemic isolated rat heart was studied. Five minutes of total global ischemia without reperfusion produced a significant depression in adenine nucleotide translocase in subsarcolemmal mitochondria (SLM), whereas a minimum of 10 min ischemia was required to observe a significant depression in interfibrillar mitochondria (IFM). Increasing durations of ischemia resulted in a progressively larger depression in translocase activity, with a maximum depression of approximately 75% seen in both populations following 20 min ischemia. In contrast, oxidative phosphorylation was totally unaffected in either mitochondrial population following up to 20 min of ischemia. We assessed whether translocase activity or oxidative phosphorylation were related to contractile recovery in hearts reperfused following various durations of ischemia. In SLM, translocase activity was further depressed following reperfusion compared with pre-reperfusion ischemic values, whereas with IFM only reperfusion following 5 min ischemia produced a further depression in translocase values. Oxidative phosphorylation rates of SLM and IFM were significantly depressed following reperfusion of ischemic hearts, although SLM exhibited a generally higher sensitivity in this regard. In reperfused hearts, an overall significant relationship was found between oxidative phosphorylation rate and adenine translocase activity as well as between translocase activity and post-reperfusion contractile recovery. These data show that ischemia can produce a significant depression in translocase activity in the absence of any change in oxidative phosphorylation. The results also suggest that the depression in mitochondrial ADP/ATP translocase and subsequent inhibition of oxidative phosphorylation in the reperfused heart may represent one of the important contributory mechanisms involved in cardiac failure and injury during acute ischemia and reperfusion.Key words: myocardial ischemia, myocardial reperfusion, mitochondria, oxidative phosphorylation, adenine nucleotide translocase.

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