Ethanolamine and phosphoethanolamine inhibit mitochondrial function in vitro: implications for mitochondrial dysfunction hypothesis in depression and bipolar disorder.
BACKGROUND
A growing body of experimental evidence suggests that mitochondrial dysfunction, including alterations in phospholipid metabolism, might be involved in the pathophysiology of affective illnesses, such as depression and bipolar disorder. The purpose of this study was to determine whether the phosphomonoester phosphoethanolamine (PE) and the lipid metabolite choline (Cho), which are known to be altered in depression and bipolar disorder, and/or their precursors/metabolites, might directly affect mitochondrial bioenergetic function in vitro.


METHODS
To this end, rates of oxygen consumption in freshly isolated, intact mitochondria were determined polarographically in the presence and absence of PE, Cho, ethanolamine (Etn), glycerophosphoethanolamine (GPE), and glycerophosphocholine (GPC).


RESULTS
The data demonstrate that PE and Etn inhibit mitochondrial respiratory activity in a dose-dependent manner, whereas Cho, GPC, and GPE have no measurable effect on bioenergetic function.


CONCLUSIONS
This reflects a specific inhibition by Etn and PE on mitochondrial function rather than a more generalized phenomenon induced by similarities in structure between the lipid metabolites. These results also suggest a possible relationship between mitochondrial dysfunction and altered phospholipid metabolism in the brains of patients with depression and bipolar disorder.
Modica-Napolitano
Josephine S
JS
Department of Biology, Merrimack College, 315 Turnpike Street, North Andover, MA 01845, USA.
Renshaw
Perry F
PF
D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019856:Ethanolamine / Q000378:metabolism* / Q000494:pharmacology; D004983:Ethanolamines / Q000378:metabolism* / Q000494:pharmacology; D005997:Glycerylphosphorylcholine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004983:Ethanolamines; D010714:Phosphatidylethanolamines; C002449:glycerophosphoethanolamine; D019856:Ethanolamine; D005997:Glycerylphosphorylcholine; C005448:phosphorylethanolamine; D002794:Choline