BIOMATERIALS
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2024
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IF 12.8
Yucheng Ji,Yuwei Hu,Yubo Feng,Lei Liu,Zhanyi Chen,Hongxing Shen,Yingchao Han,He Xu,Lifeng Lao
Currently, mitochondrial dysfunction caused by oxidative stress is a growing concern in degenerative diseases, notably intervertebral disc degeneration (IVDD). Dysregulation of the balance of mitochondrial quality control (MQC) has been considered the key contributor, while it’s still challenging to effectively harmonize different MQC components in a simple and biologically safe way. Hydrogen gas (H 2 ) is a promising mitochondrial therapeutic molecule due to its bio-reductivity and diffusibility across cellular membranes, yet its relationship with MQC regulation remains unknown. Herein, we propose a mitochondrial ‘Birth-Death’ coordinator achieved by an intelligent hydrogen nanogenerator (Fe@HP-OD), which can sustainably release H 2 in response to the unique microenvironment in degenerated IVDs. Both in vitro and in vivo results prove alleviation of cellular oxidative stress and restoration of nucleus pulposus cells function, thereby facilitating successful IVD regeneration. Significantly, this study for the first time proposes the mitochondrial ‘Birth-Death’ coordination mechanism: 1) attenuation of overactivated mitochondrial ‘Death’ process (UPR mt and unselective mitophagy); and 2) activation of Adenosine 5‘-monophosphate-activated protein kinase (AMPK) signaling pathway for mitochondrial ‘Birth-Death’ balance (mitochondrial biogenesis and controlled mitophagy). These pioneering findings can fill in the gaps in molecular mechanisms for H 2 regulation on MQC homeostasis, and pave the way for future strategies towards restoring equilibrium of MQC system against degenerative diseases.
研究领域:
生物医学工程
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再生医学
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分子生物学
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纳米技术
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
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2025
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IF 14.1
Shuoting Zhou,Xi Xiong,Jialong Hou,Qi Duan,Yi Zheng,Tao Jiang,Jiani Huang,Haijun He,Jiaxue Xu,Keke Chen,Wenwen Wang,Jinlai Cai,Jingjing Qian,Huijun Chen,Weihong Song,XinShi Wang,Chenglong Xie
Serving as a pivotal hub for cellular metabolism and intracellular signaling, the mitochondrion has emerged as a crucial organelle whose dysfunction is linked to many human diseases, including neurodegenerative disorders, particularly Parkinson's disease (PD). However, whether mitochondrial quality control (MQC) can be targeted for therapeutic interventions remains uncertain. This study uses clinical samples, molecular biology techniques, pharmacological interventions, and genetic approaches to investigate the significance of NAD+ levels in cross-species models of PD. These results reveal that treatment of rotenone-incubated cells with NAD+ boosters (such as NMN, siCD38, and NAT) increases UPR mt /mitophagy-related MQC, reduces pro-inflammatory cytokine expression, inhibits apoptosis, and strengthen redox reactions. In vivo, NMN supplementation inhibits motor deficit and forestalls the neuropathological phenotypes of MPTP-induced PD mice, which are required for the atf4-related mitochondrial UPR pathway. Notably, bulk omics signatures and metabolomic profiling analyses of the striatum reveal NMN-induced transcriptional changes in genes and proteins involved in mitochondrial homeostasis. Thus, these findings demonstrate that the accelerated pathology in PD models is probably mediated by impaired MQC and that bolstering cellular NAD+ levels alleviates mitochondrial proteotoxic stress and mitigate PD phenotypes.
研究领域:
神经科学
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细胞生物学
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药理学
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分子生物学
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生物化学
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基因组学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）