Glial swip-10 controls systemic mitochondrial function, oxidative stress, and neuronal viability via copper ion homeostasis

• 成果类型: Article
• 署名作者: Rodriguez, Peter; Kalia, Vrinda; Fenollar-Ferrer, Cristina; Gibson, Chelsea L.; Gichi, Zayna; Rajoo, Andre; Matier, Carson D.; Pezacki, Aidan T.; Xiao, Tong; Carvelli, Lucia; Chang, Christopher J.; Miller, Gary W.; V. Khamoui, Andy; Boerner, Jana; Blakely, Randy D.
• 署名单位: Columbia University; National Institutes of Health (NIH) - USA; NIH National Institute on Deafness & Other Communication Disorders (NIDCD); State University System of Florida; Florida Atlantic University; Oak Ridge Associated Universities; United States Department of Energy (DOE); Oak Ridge Institute for Science & Education; State University System of Florida; Florida Atlantic University; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Princeton University; State University System of Florida; Florida Atlantic University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11827
• DOI: 10.1073/pnas.2320611121
• 发表日期: 2024-09-24
• 关键词: parkinsons-disease; dopamine neurons; affinity; hormone; pink1; cells; zinc

摘要

Cuprous copper [Cu(I)] is an essential cofactor for enzymes that support many fundamental cellular functions including mitochondrial respiration and suppression of oxidative stress. Neurons are particularly reliant on mitochondrial production of ATP, with many neurodegenerative diseases, including Parkinson's disease, associated with diminished mitochondrial function. The gene MBLAC1 encodes a ribonuclease that to reduce Cu(II) to Cu(I), and when mutated disrupt ATP production, elevates oxidative stress, and severely impacts cell growth. Whether this process supports neuronal and/or systemic physiology in higher eukaryotes is unknown. Previously, we identified swip- 10, swip- 10 in limiting dopamine (DA) neuron excitability and sustaining DA neuron viastructure mirrors that of MBLAC1 and locates a loss of function coding mutation at a biochemical, and pharmacological studies that deletion of swip- 10 in worms negatively