Mitochondria modulate programmed neuritic retraction
Baranov S. V., Baranova O. V., Yablonska S., Suofu Y., Vazquez A. L., Kozai T. D. Y., Tracy C. X., Ferrando L. M., Larkin T. M., Tyurina Y. Y., Kagan V. E., Carlisle D. L., Kristal B. S., Friedlander R. M.
Proceedings of the National Academy of Sciences of the United States of America
Vol.116, Issue2, P. 650-659
Опубликовано: 2019
Тип ресурса: Статья
DOI:10.1073/pnas.1811021116
Аннотация:
Neuritic retraction in the absence of overt neuronal death is a shared feature of normal aging and neurodegenerative disorders, but the intracellular mechanisms modulating this process are not understood. We propose that cumulative distal mitochondrial protein damage results in impaired protein import, leading to mitochondrial dysfunction and focal activation of the canonical apoptosis pathway in neurites. This is a controlled process that may not lead to neuronal death and, thus, we term this phenomenon “neuritosis.” Consistent with our hypothesis, we show that in primary cerebrocortical neurons, mitochondrial distance from the soma correlates with increased mitochondrial protein damage, PINK1 accumulation, reactive oxygen species production, and decreased mitochondrial membrane potential and depolarization threshold. Furthermore, we demonstrate that the distance-dependent mitochondrial membrane potential gradient exists in vivo in mice. We demonstrate that impaired distal mitochondri
Ключевые слова:
Caspase-3; Mitochondrial membrane potential; Mutant huntingtin; Neurite retraction; Neurodegeneration
caspase 3; mitochondrial protein; PINK1 protein; reactive oxygen metabolite; unclassified drug; Casp3 protein, mouse; caspase 3; protein kinase; PTEN-induced putative kinase; reactive oxygen metabolite; adult; aging; animal cell; animal experiment; animal tissue; Article; brain cell; cell activation; cell death; controlled study; disorders of mitochondrial functions; enzyme activation; enzyme activity; human; in vitro study; in vivo study; mitochondrial membrane potential; mitochondrion; mouse; nerve cell characteristics and functions; nerve cell membrane steady potential; nerve cell necrosis; nerve cell plasticity; nerve degeneration; neurite; neuritic retraction; neuroapoptosis; nonhuman; priority journal; stress; synaptosome; animal; apoptosis; degenerative disease; genetics; metabolism; mitochondrial membrane potential; mitochondrion; pathology; transgenic mouse; Animals; Apoptosis; Caspase 3; Membrane Potential, Mitochondrial; Mice; Mice, Transgenic; Mitochondria; Neurites; Neurod
Язык текста: Английский
ISSN: 1091-6490
Baranov S. V.
Baranova O. V.
Yablonska S.
Suofu Y.
Vazquez A. L.
Kozai T. D. Y.
Tracy C. X. Cui X.
Ferrando L. M.
Larkin T. M.
Tyurina Y. Y.
Kagan V. E. Valerian E 1946-
Carlisle D. L.
Kristal B. S.
Friedlander R. M.
Баранов С. В.
Баранова О. В.
Яблонска С.
Суофу Y.
Вазqуез А. Л.
Козаи Т. Д. Y.
Траcy C. Х. Cуи Х.
Феррандо Л. М.
Ларкин Т. М.
Тюрина Y. Y.
Каган В. Е. Валериан Е 1946-
Cарлисле Д. Л.
Кристал Б. С.
Фриедландер Р. М.
Mitochondria modulate programmed neuritic retraction
Текст визуальный непосредственный
Proceedings of the National Academy of Sciences of the United States of America
Proquest Academic Research Library
Vol.116, Issue2 P. 650-659
2019
Статья
Caspase-3 Mitochondrial membrane potential Mutant huntingtin Neurite retraction Neurodegeneration
caspase 3 mitochondrial protein PINK1 protein reactive oxygen metabolite unclassified drug Casp3 protein, mouse caspase 3 protein kinase PTEN-induced putative kinase reactive oxygen metabolite adult aging animal cell animal experiment animal tissue Article brain cell cell activation cell death controlled study disorders of mitochondrial functions enzyme activation enzyme activity human in vitro study in vivo study mitochondrial membrane potential mitochondrion mouse nerve cell characteristics and functions nerve cell membrane steady potential nerve cell necrosis nerve cell plasticity nerve degeneration neurite neuritic retraction neuroapoptosis nonhuman priority journal stress synaptosome animal apoptosis degenerative disease genetics metabolism mitochondrial membrane potential mitochondrion pathology transgenic mouse Animals Apoptosis Caspase 3 Membrane Potential, Mitochondrial Mice Mice, Transgenic Mitochondria Neurites Neurod
Neuritic retraction in the absence of overt neuronal death is a shared feature of normal aging and neurodegenerative disorders, but the intracellular mechanisms modulating this process are not understood. We propose that cumulative distal mitochondrial protein damage results in impaired protein import, leading to mitochondrial dysfunction and focal activation of the canonical apoptosis pathway in neurites. This is a controlled process that may not lead to neuronal death and, thus, we term this phenomenon “neuritosis.” Consistent with our hypothesis, we show that in primary cerebrocortical neurons, mitochondrial distance from the soma correlates with increased mitochondrial protein damage, PINK1 accumulation, reactive oxygen species production, and decreased mitochondrial membrane potential and depolarization threshold. Furthermore, we demonstrate that the distance-dependent mitochondrial membrane potential gradient exists in vivo in mice. We demonstrate that impaired distal mitochondri