Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice
Cole L. K., Kim J. H., Amoscato A. A., Tyurina Y. Y., Bayır H., Karimi B., Siddiqui T. J., Kagan V. E., Hatch G. M., Kauppinen T. M.
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Vol.1864, Issue10, P. 3353-3367
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1016/j.bbadis.2018.07.022
Аннотация:
Cardiolipin (CL) is a key mitochondrial phospholipid essential for mitochondrial energy production. CL is remodeled from monolysocardiolipin (MLCL) by the enzyme tafazzin (TAZ). Loss-of-function mutations in the gene which encodes TAZ results in a rare X-linked disorder called Barth Syndrome (BTHS). The mutated TAZ is unable to maintain the physiological CL:MLCL ratio, thus reducing CL levels and affecting mitochondrial function. BTHS is best known as a cardiac disease, but has been acknowledged as a multi-syndrome disorder, including cognitive deficits. Since reduced CL levels has also been reported in numerous neurodegenerative disorders, we examined how TAZ-deficiency impacts cognitive abilities, brain mitochondrial respiration and the function of hippocampal neurons and glia in TAZ knockdown (TAZ kd) mice. We have identified for the first time the profile of changes that occur in brain phospholipid content and composition of TAZ kd mice. The brain of TAZ kd mice exhibited reduced T
Ключевые слова:
Barth syndrome; Brain; Cardiolipin; Cognition; Hippocampus; Monolysocardiolipin; Tafazzin
cardiolipin; cytochrome c oxidase; enzyme; lysophospholipid; phosphatidylglycerol; phosphatidylglycerol synthase; protein tyrosine phosphatase; protein tyrosine phosphatase localized to mitochondrion 1; reactive oxygen metabolite; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone); succinate dehydrogenase (ubiquinone); synaptophysin; tafazzin; TATA binding protein; transcription factor IIB; ubiquinol cytochrome c reductase; unclassified drug; cardiolipin; lysophospholipid; monolysocardiolipin; reactive oxygen metabolite; synaptophysin; Syp protein, mouse; Taz protein, mouse; transcription factor; animal experiment; animal model; animal tissue; Article; bioaccumulation; brain function; brain mitochondrion; cognition; cognitive defect; comparative study; controlled study; disease association; glia; hippocampal CA1 region; hippocampus; immunocompetent cell; lipid composition; male; memory disorder; microglia; mitochondrial respiration; molecule; motor performance; mouse
Язык текста: Английский
ISSN: 0925-4439
Cole L. K.
Kim J. H.
Amoscato A. A.
Tyurina Y. Y.
Bayır H.
Karimi B.
Siddiqui T. J.
Kagan V. E. Valerian E 1946-
Hatch G. M.
Kauppinen T. M.
Cоле Л. К.
Ким Й. Х.
Амосcато А. А.
Тюрина Y. Y.
Байıр Х.
Карими Б.
Сиддиqуи Т. Й.
Каган В. Е. Валериан Е 1946-
Хатч Г. М.
Кауппинен Т. М.
Aberrant cardiolipin metabolism is associated with cognitive deficiency and hippocampal alteration in tafazzin knockdown mice
Текст визуальный непосредственный
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Elsevier Science Publisher B.V.
Vol.1864, Issue10 P. 3353-3367
2018
Статья
Barth syndrome Brain Cardiolipin Cognition Hippocampus Monolysocardiolipin Tafazzin
cardiolipin cytochrome c oxidase enzyme lysophospholipid phosphatidylglycerol phosphatidylglycerol synthase protein tyrosine phosphatase protein tyrosine phosphatase localized to mitochondrion 1 reactive oxygen metabolite reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) succinate dehydrogenase (ubiquinone) synaptophysin tafazzin TATA binding protein transcription factor IIB ubiquinol cytochrome c reductase unclassified drug cardiolipin lysophospholipid monolysocardiolipin reactive oxygen metabolite synaptophysin Syp protein, mouse Taz protein, mouse transcription factor animal experiment animal model animal tissue Article bioaccumulation brain function brain mitochondrion cognition cognitive defect comparative study controlled study disease association glia hippocampal CA1 region hippocampus immunocompetent cell lipid composition male memory disorder microglia mitochondrial respiration molecule motor performance mouse
Cardiolipin (CL) is a key mitochondrial phospholipid essential for mitochondrial energy production. CL is remodeled from monolysocardiolipin (MLCL) by the enzyme tafazzin (TAZ). Loss-of-function mutations in the gene which encodes TAZ results in a rare X-linked disorder called Barth Syndrome (BTHS). The mutated TAZ is unable to maintain the physiological CL:MLCL ratio, thus reducing CL levels and affecting mitochondrial function. BTHS is best known as a cardiac disease, but has been acknowledged as a multi-syndrome disorder, including cognitive deficits. Since reduced CL levels has also been reported in numerous neurodegenerative disorders, we examined how TAZ-deficiency impacts cognitive abilities, brain mitochondrial respiration and the function of hippocampal neurons and glia in TAZ knockdown (TAZ kd) mice. We have identified for the first time the profile of changes that occur in brain phospholipid content and composition of TAZ kd mice. The brain of TAZ kd mice exhibited reduced T