Mitochondrial NO and reactive nitrogen species production: does mtNOS exist?
It is more than 10 years now that mitochondria are suspected to be sources of nitric oxide (NO). This hypothesis is intriguing since NO has multiple targets within the organelle and it is even suggested that mitochondria are the primary targets of NO in the cell. Most remarkably, nanomolar concentrations of NO can inhibit mitochondrial respiration, so even a small amount of NO in the mitochondrial matrix may regulate ATP synthesis. Therefore, the idea that mitochondria themselves are capable of NO production is an important concept in several physiological and pathological mechanisms. However, this field of research generates surprisingly few original papers and the published studies contain conflicting results. The reliability of the results is frequently questioned since they are seldom reproduced by independent investigators. Until 2003, all papers published in this field showed affirmative results but since then several studies directly challenged the existence of a mitochondrial nitric oxide synthase. The present review aims to summarize the most recent developments in mitochondrial NO production, highlights a few unsolved questions, and proposes new directions for future work in this research area.
Lacza
Zsombor
Z
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Ullöi út 78/a, 1082 Budapest, Hungary. zlacza@mac.com
Pankotai
Eszter
E
Csordás
Attila
A
Gero
Domokos
D
Kiss
Levente
L
Horváth
Eszter M
EM
Kollai
Márk
M
Busija
David W
DW
Szabó
Csaba
C
D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D018384:Oxidative Stress; D026361:Reactive Nitrogen Species / Q000096:biosynthesis*
D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II