Related Experiment Video
Updated: May 24, 2026
08:23
Chemiluminescence-based Assays for Detection of Nitric Oxide and its Derivatives from Autoxidation and Nitrosated Compounds
Published on: February 16, 2022
Mitochondria and nitric oxide: chemistry and pathophysiology
Paolo Sarti1, Marzia Arese, Elena Forte
1Department of Biochemical Sciences, University of Rome, Rome, Italy. paolo.sarti@uniroma1.it
Advances in Experimental Medicine and Biology
|March 9, 2012
Summary
Nitric oxide (NO) affects cell respiration by inhibiting Complex I and Complex IV. The specific inhibition pathway depends on NO concentration, exposure time, and cellular conditions, influencing cellular energy production.
Area of Science:
- Biochemistry
- Cellular Respiration
- Mitochondrial Function
Background:
- Nitric oxide (NO) is a key signaling molecule that regulates various physiological processes.
- NO interacts with mitochondrial respiratory chain complexes, impacting cellular energy production.
- Complex I and Complex IV are primary targets of NO in the electron transport chain.
Purpose of the Study:
- To elucidate the distinct mechanisms by which NO inhibits Complex I and Complex IV.
- To investigate the factors determining the prevalence of different NO inhibition pathways.
- To assess the role of mitochondrial cytochrome c in NO-mediated respiratory inhibition.
Main Methods:
- Studied the kinetics and mechanisms of NO interaction with isolated respiratory complexes.
- Utilized cell cultures (SH-SY5Y neuroblastoma, lymphoid cells) under varying oxygen tensions.
- Analyzed the formation of NO adducts (nitrosyl and nitrite derivatives) with cytochrome c oxidase (CcOX).
Main Results:
- Complex IV inhibition by NO is rapid, reversible, and occurs at nanomolar concentrations.
- Complex I inhibition requires prolonged exposure to higher NO concentrations and involves S-nitrosation of the ND3 subunit.
- Two distinct CcOX-NO adducts were identified, with their formation dependent on electron flux and substrate availability.
- Cellular conditions influenced whether NO was degraded to nitrite or formed a stable CcOX-NO adduct.
Conclusions:
- Mitochondrial cytochrome c levels may dictate the predominant NO-induced respiratory inhibition pathway in vivo.
- Understanding these interactions is crucial for comprehending cellular responses to nitrosative stress.
- NO's modulation of respiratory complexes has significant patho-physiological implications.
Related Concept Videos
01:28Nitric Oxide Signaling Pathway
Nitric oxide (NO), an inorganic gas, acts as a potent second messenger in most animal and plant tissues. NO diffuses out of the cells that produce it and enters the neighboring cells to generate a downstream response. NO synthase (NOS) catalyzes NO production by the deamination of the amino acid arginine. There are three isoforms of NOS. Endothelial cells have endothelial NOS (eNOS), nerve and muscle cells have neuronal NOS (nNOS), and macrophages produce inducible NOS (iNOS) upon exposure to...
01:45Mitochondrial Membranes
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
01:45Mitochondrial Membranes
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
01:26Coronary Artery Disease II: Pathophysiology
Coronary Artery Disease (CAD) originates from a series of events that impair the function of coronary arteries, the blood vessels responsible for delivering oxygen-rich blood to the heart muscle. The pathophysiology of CAD is closely linked to atherosclerosis, a chronic inflammatory and lipid-driven condition affecting the vascular endothelium.1. Endothelial DamageThe process begins with damage to the vascular endothelium, which serves as a protective barrier between the blood and the vessel...
01:28The Inner Mitochondrial Membrane
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...