线粒体NAD+再生的遗传调节不能阻止线粒体复合体I损伤引起的多巴胺能神经元功能障碍。

IF 4.6 2区生物学 Q2 CELL BIOLOGY

Frontiers in Cell and Developmental Biology Pub Date : 2025-09-25 eCollection Date: 2025-01-01 DOI:10.3389/fcell.2025.1650462

Karis B D'Alessandro, Enrico Zampese, Jenna L E Blum, Britta Kuusik, Alec Palmiotti, Shawn M Davidson, Colleen R Reczek, D James Surmeier, Navdeep S Chandel

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引用次数: 0

摘要

线粒体复合体I （MCI）的功能障碍与帕金森病多巴胺能神经元的退化有关。在这里，我们报道了表达MitoLbNOX（细菌酶LbNOX的线粒体靶向版本）在MCI受损的多巴胺能神经元（MCI- park小鼠）中增加线粒体中NAD+的再生以维持NAD+/NADH比率的作用。MitoLbNOX的表达并不能改善MCI- park小鼠的细胞或行为缺陷，这表明线粒体NAD+/NADH比值的改变不足以补偿多巴胺能神经元MCI功能的丧失。

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Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment.

Dysfunction of mitochondrial complex I (MCI) has been implicated in the degeneration of dopaminergic neurons in Parkinson's disease. Here, we report the effect of expressing MitoLbNOX, a mitochondrial-targeted version of the bacterial enzyme LbNOX, which increases regeneration of NAD+ in the mitochondria to maintain the NAD+/NADH ratio, in dopaminergic neurons with impaired MCI (MCI-Park mice). MitoLbNOX expression did not ameliorate the cellular or behavioral deficits observed in MCI-Park mice, suggesting that alteration of the mitochondrial NAD+/NADH ratio alone is not sufficient to compensate for loss of MCI function in dopaminergic neurons.

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来源期刊

Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

9.70

自引率

3.60%

发文量

2531

审稿时长

12 weeks

期刊介绍： Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.