Nitric Oxide Potently and Reversibly Deenergizes Mitochondria at Low Oxygen Tension

Schweizer, Matthias; Richter, Christoph

doi:10.1006/bbrc.1994.2441

Cited by 312 publications

(173 citation statements)

References 0 publications

Supporting

Mentioning

164

Contrasting

Unclassified

Order By: Relevance

“…Goadsby et al (1992) first demonstrated that NO links changes in CBF and metabolism, at least for spreading depressionelicited increases in metabolic activity, and the results implied that NO may have a more general role in flow-metabolism coupling (Moncada and Erusalimsky, 2002). Brown and Cooper (1994), Cleeter et al (1994), and Schweizer and Richter (1994) first reported that cytochrome c oxidation can be inhibited by NO. Brown (1995) proposed that NO may be the physiologic regulator of the affinity of mitochondrial respiration for oxygen, enabling mitochondria to act as sensors of oxygen over the entire physiologic range.…”

Section: Nitric Oxidementioning

confidence: 99%

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Gjedde

Johannsen

Cold

et al. 2005

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

The reactions of cerebral metabolism to imposed changes of cerebral blood flow (CBF) are poorly understood. A common explanation of the mismatched CBF and oxygen consumption (CMR O 2 ) during neuronal excitation holds that blood flow rises more than oxygen consumption to compensate for an absent oxygen reserve in brain mitochondria. The claim conversely implies that oxygen consumption must decline when blood flow declines. As the prevailing rate of reaction of oxygen with cytochrome c oxidase is linked to the tension of oxygen, the claim fails to explain how oxygen consumption is maintained during moderate reductions of CBF imposed by hyperventilation (hypocapnia) or cyclooxygenase (COX) inhibition. To resolve this contradiction, we extended the previously published oxygen delivery model with a term allowing for the adjustment of the affinity of cytochrome c oxidase to a prevailing oxygen tension. The extended model predicted constant oxygen consumption at moderately reduced blood flow. We determined the change of affinity of cytochrome c oxidase in the extended model by measuring CBF in seven, and CMR O 2 in five, young healthy volunteers before and during COX inhbition with indomethacin. The average CBF declined 35%, while neither regional nor average CMR O 2 changed significantly. The adjustment of cytochrome c oxidase affinity to the declining oxygen delivery could be ascribed to a hypothetical factor with several properties in common with nitric oxide.

show abstract

Section: Nitric Oxidementioning

confidence: 99%

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Gjedde

Johannsen

Cold

et al. 2005

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…1). The reversible NO inhibition of cytochrome oxidase occurs at nanomolar levels of NO (11)(12)(13), so that NO is potentially a physiological regulator of respiration (3,(14)(15)(16)(17). NO inhibits by reacting with either the reduced or oxidised binuclear (oxygen-binding ) site of cytochrome oxidase to give either cytochrome a 3 2C -NO or cytochrome a 3 3C -NO 2 ¡ (18)(19)(20).…”

Section: No Actions On Mitochondriamentioning

confidence: 99%

“…Endogenously produced NO may tonically inhibit respiration at cytochrome oxidase in some cells (21,22). Inhibition is in competition with oxygen, so that NO can dramatically increase the apparent K m of respiration for oxygen (2,(12)(13)(14). Thus, NO can make cells effectively hypoxic at relatively high oxygen levels, and potentially sensitise tissues to hypoxic damage.…”

Section: No Actions On Mitochondriamentioning

confidence: 99%

Nitric Oxide, Mitochondria, and Cell Death

Brown¹,

Borutaitė²

2001

IUBMB Life

158

102

View full text Add to dashboard Cite

show abstract

“…Several reports have shown that NO added to the mitochondria causes a reversible COX inhibition even at low oxygen concentrations. For example, 1.3 lM NO added to isolated mitochondria reversibly inhibited COX and decreased the mitochondrial respiration and transmembrane potential (15). Altering the ratio between COX content and NO concentration alters the degree of inhibition of mitochondrial respiration.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide irreversibly inhibits cytochrome oxidase at low oxygen concentrations: Evidence for inverse oxygen concentration‐dependent peroxynitrite formation

2007

View full text Add to dashboard Cite

SummaryThe present study shows that nitric oxide (NO) irreversibly inhibits purified cytochrome oxidase in a reverse oxygen concentration-dependent manner. The inhibition is dramatically protected by a peroxynitrite scavenger, suggesting that peroxynitrite is formed from the reaction of NO with cytochrome oxidase at low oxygen concentration, and that peroxynitrite is involved in irreversible cytochrome oxidase inactivation. Production of nitroxyl anion or superoxide was tested as potential mechanisms underlying the conversion of NO to peroxynitrite. A nitroxyl anion scavenger potently protected the irreversible inhibition, whereas a superoxide dismutase did not provide protective effect, suggesting that the peroxynitrite was formed from nitroxyl anion rather than the reaction of NO with superoxide. IUBMBIUBMB Life, 60(1): [64][65][66][67] 2008

show abstract

Nitric Oxide Potently and Reversibly Deenergizes Mitochondria at Low Oxygen Tension

Cited by 312 publications

References 0 publications

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Cerebral Metabolic Response to Low Blood Flow: Possible Role of Cytochrome Oxidase Inhibition

Nitric Oxide, Mitochondria, and Cell Death

Nitric oxide irreversibly inhibits cytochrome oxidase at low oxygen concentrations: Evidence for inverse oxygen concentration‐dependent peroxynitrite formation

Contact Info

Product

Resources

About