BRIEF RESEARCH REPORT article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1650462
This article is part of the Research TopicBeyond Energy Production: Exploring Mitochondrial Dynamics and DiseaseView all 4 articles
Genetic modulation of mitochondrial NAD+ regeneration does not prevent dopaminergic neuron dysfunction caused by mitochondrial complex I impairment
Provisionally accepted
Karis B. D'Alessandro1
Enrico Zampese1Jenna L.E. Blum1Britta Kuusik2Alec Palmiotti1Shawn M. Davidson1Colleen R. Reczek1
D. James Surmeier1
Navdeep S. Chandel1*- 1Northwestern University, Evanston, United States
- 2Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, United States
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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.
Keywords: Parkinson's disease, NAD+, neurometabolism, neurodegeneration, Mitochondrial Complex I, Dopaminergic Neurons
Received: 19 Jun 2025; Accepted: 09 Sep 2025.
Copyright: © 2025 D'Alessandro, Zampese, Blum, Kuusik, Palmiotti, Davidson, Reczek, Surmeier and Chandel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Navdeep S. Chandel, Northwestern University, Evanston, United States
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