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Nitric oxide inhibits enterocyte mitochondrial phospholipase D
M Madesh1, K A Balasubramanian
1The Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College Hospital, Vellore, India.
Abstract:
Mitochondrial damage is one of the prominent features of cell death in oxidative stress and related pathological conditions. Alteration in membrane lipid composition may be responsible for the mitochondrial damage. In this study, we have shown that intestinal mitochondria contain an active phospholipase D (PLD) which is activated by oxidants, Ca2+ or polyamines and this results in degradation of phosphatidylethanolamine (PE) and formation of phosphatidic acid (PA). This PLD activity is inhibited by nitric oxide (NO) which prevents the lipid alteration in mitochondria when exposed to these agents. This can be reversed by the NO scavenger, haemoglobin. This suggests that alteration of mitochondrial membrane lipid composition by activation of PLD in certain pathological condition such as oxidative stress may be prevented by the simultaneous presence of nitric oxide.
Insights
Oxidative stress damages mitochondria via phospholipase D (PLD) activation, altering membrane lipids. Nitric oxide (NO) inhibits this PLD activity, preventing mitochondrial damage and suggesting a protective role in pathological conditions.
Area of Science:
- Biochemistry
- Cell Biology
- Pathology
Background:
- Mitochondrial damage is a key feature of cell death in oxidative stress and related diseases.
- Changes in mitochondrial membrane lipid composition are implicated in this damage.
Purpose of the Study:
- To investigate the role of phospholipase D (PLD) in mitochondrial membrane lipid alteration.
- To determine the effect of nitric oxide (NO) on oxidant-induced mitochondrial damage.
Main Methods:
- Assessed intestinal mitochondrial phospholipase D (PLD) activity.
- Investigated the effects of oxidants, Ca2+, polyamines, and nitric oxide (NO) on mitochondrial lipids.
- Utilized haemoglobin as a nitric oxide scavenger.
Main Results:
- Intestinal mitochondria possess an active PLD, activated by oxidants, Ca2+, or polyamines, leading to phosphatidylethanolamine (PE) degradation and phosphatidic acid (PA) formation.
- Nitric oxide (NO) inhibited PLD activity, preventing lipid alteration.
- Haemoglobin reversed the NO-mediated inhibition, confirming NO's role.
Conclusions:
- Oxidant-induced activation of mitochondrial PLD alters membrane lipid composition, contributing to mitochondrial damage.
- Nitric oxide (NO) protects mitochondria by inhibiting PLD activity.
- NO may prevent mitochondrial damage in pathological conditions involving oxidative stress.