Hexokinase 2 interacts with PINK1 to facilitate mitophagy in astrocytes and restrain inflammation-induced neurotoxicity.

IF 7.5 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-06-17 DOI:10.1016/j.celrep.2025.115809

Jack H Howden, Hanna Hakansson, Manuela Nieto-Rostro, Robyn McAdam, Charles Arber, Nicholas J Brandon, Josef T Kittler

引用次数: 0

Abstract

Mitochondria are essential for ATP production, calcium buffering, and apoptotic signaling, with mitophagy playing a critical role in removing dysfunctional mitochondria. This study demonstrates that PINK1-dependent mitophagy occurs more rapidly and is less spatially restricted in astrocytes compared to neurons. We identified hexokinase 2 (HK2) as a key regulator of mitophagy in astrocytes, forming a glucose-dependent complex with PINK1 in response to mitochondrial damage. Additionally, exposure to neuroinflammatory stimuli enhances PINK1/HK2-dependent mitophagy, providing neuroprotection. These findings contribute to our understanding of mitophagy mechanisms in astrocytes and underscore the importance of PINK1 in cellular health and function within the context of neurodegenerative diseases.

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己糖激酶2与PINK1相互作用，促进星形胶质细胞的自噬，抑制炎症诱导的神经毒性。

线粒体对ATP的产生、钙缓冲和凋亡信号传导至关重要，线粒体自噬在去除功能失调的线粒体中起着关键作用。这项研究表明，与神经元相比，星形胶质细胞中依赖pink1的有丝分裂发生得更快，空间限制更少。我们发现己糖激酶2 （HK2）是星形胶质细胞线粒体自噬的关键调节因子，在线粒体损伤时与PINK1形成葡萄糖依赖性复合物。此外，暴露于神经炎症刺激可增强PINK1/ hk2依赖性的有丝分裂，从而提供神经保护。这些发现有助于我们理解星形胶质细胞的线粒体自噬机制，并强调了PINK1在神经退行性疾病背景下对细胞健康和功能的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.