دورية أكاديمية
أعرض في EDS

Trehalose enhances mitochondria deficits in human NPC1 mutant fibroblasts but disrupts mouse Purkinje cell dendritic growth ex vivo.

التفاصيل البيبلوغرافية
العنوان: Trehalose enhances mitochondria deficits in human NPC1 mutant fibroblasts but disrupts mouse Purkinje cell dendritic growth ex vivo.
المؤلفون: MacLeod CM; Department of Biology, Providence College, Providence, RI, United States of America., Yousufzai FAK; Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ, United States of America., Spencer LT; Department of Biology, Providence College, Providence, RI, United States of America., Kim S; Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ, United States of America., Rivera-Rosario LA; Department of Biology, Providence College, Providence, RI, United States of America., Barrera ZD; Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ, United States of America., Walsh L; Department of Biology, Providence College, Providence, RI, United States of America., Krummenacher C; Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ, United States of America., Carone B; Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ, United States of America., Soto I; Department of Biology, Providence College, Providence, RI, United States of America.
المصدر: PloS one [PLoS One] 2023 Nov 30; Vol. 18 (11), pp. e0294312. Date of Electronic Publication: 2023 Nov 30 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Mitochondria*/metabolism , Niemann-Pick Disease, Type C*/drug therapy , Niemann-Pick Disease, Type C*/genetics , Niemann-Pick Disease, Type C*/metabolism , Trehalose*/pharmacology, Animals ; Humans ; Mice ; Cholesterol/metabolism ; Fibroblasts/metabolism ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Lysosomes/metabolism ; Niemann-Pick C1 Protein ; Purkinje Cells/pathology
مستخلص: Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol accumulation that leads to early neurodegeneration in Niemann-Pick type C (NPC) disease. Mitochondria pathology and deficits in NPC1 deficient cells are associated with impaired lysosomal proteolysis and metabolic signaling. It is thought that activation of the transcription factor TFEB, an inducer of lysosome biogenesis, restores lysosomal-autophagy activity in lysosomal storage disorders. Here, we investigated the effect of trehalose, a TFEB activator, in the mitochondria pathology of NPC1 mutant fibroblasts in vitro and in mouse developmental Purkinje cells ex vivo. We found that in NPC1 mutant fibroblasts, serum starvation or/and trehalose treatment, both activators of TFEB, reversed mitochondria fragmentation to a more tubular mitochondrion. Trehalose treatment also decreased the accumulation of Filipin+ cholesterol in NPC1 mutant fibroblasts. However, trehalose treatment in cerebellar organotypic slices (COSCs) from wild-type and Npc1nmf164 mice caused mitochondria fragmentation and lack of dendritic growth and degeneration in developmental Purkinje cells. Our data suggest, that although trehalose successfully restores mitochondria length and decreases cholesterol accumulation in NPC1 mutant fibroblasts, in COSCs, Purkinje cells mitochondria and dendritic growth are negatively affected possibly through the overactivation of the TFEB-lysosomal-autophagy pathway.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 MacLeod et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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معلومات مُعتمدة: R15 NS104994 United States NS NINDS NIH HHS
المشرفين على المادة: 97C5T2UQ7J (Cholesterol)
0 (Intracellular Signaling Peptides and Proteins)
0 (Niemann-Pick C1 Protein)
0 (NPC1 protein, human)
B8WCK70T7I (Trehalose)
تواريخ الأحداث: Date Created: 20231130 Date Completed: 20231205 Latest Revision: 20240130
رمز التحديث: 20240130
مُعرف محوري في PubMed: PMC10688965
DOI: 10.1371/journal.pone.0294312
PMID: 38033125
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0294312