有证据表明巨噬细胞中的线粒体被微自噬破坏。
Evidence that mitochondria in macrophages are destroyed by microautophagy.
作者信息
Lu Shiou-Ling, Chen Siyu, Noda Kazuya, Li Yangjie, Tsai Chao-Yuan, Omori Hiroko, Kato Yumiko, Zhang Zidi, Chen Bohan, Tokuda Kanako, Zheng Tongxin, Wakita Masahiro, Hara Eiji, Fukuda Mitsunori, Wada Yoh, Morita Eiji, Uzawa Narikazu, Murakami Shinya, Noda Takeshi
机构信息
Department of Oral Cellular Biology, Center for Frontier Oral Science, Graduate School of Dentistry, The University of Osaka, Osaka, Japan.
Department of Periodontology and Regenerative Dentistry, Graduate School of Dentistry, The University of Osaka, Osaka, Japan.
出版信息
Nat Commun. 2025 Aug 30;16(1):8123. doi: 10.1038/s41467-025-63531-x.
Microautophagy is an intracellular degradation process in which degradatory organelles, such as the lysosome, directly take up substrates by invagination and/or protrusion of their membranes. Here, we provide evidence that Rab32-positive, lysosome-related organelles in macrophages incorporate various other organelles, including endosomes and mitochondria. Our data indicates that, upon exposure to a mitochondria-damaging reagent, mitochondria can be directly engulfed by the lysosome-like organelles independently of macroautophagy or ESCRT machinery. Rab32 GTPase, phosphatidylinositol 3,5-bisphosphates, ubiquitination, and p62/SQSTM1 are crucial for this degradation. Furthermore, the degree of M1 polarization of macrophages, which is facilitated by metabolic reprogramming into increased glycolysis via mitochondrial elimination, is significantly reduced in Rab32/38 double-knockout macrophages. Thus, microautophagy plays a role in the physiological regulation of macrophages.
微自噬是一种细胞内降解过程,其中诸如溶酶体等降解细胞器通过其膜的内陷和/或突出直接摄取底物。在此,我们提供证据表明,巨噬细胞中Rab32阳性、溶酶体相关细胞器会纳入包括内体和线粒体在内的各种其他细胞器。我们的数据表明,在暴露于线粒体损伤试剂后,线粒体可被溶酶体样细胞器直接吞噬,而与巨自噬或ESCRT机制无关。Rab32 GTP酶、磷脂酰肌醇3,5-二磷酸、泛素化和p62/SQSTM1对于这种降解至关重要。此外,巨噬细胞的M1极化程度(通过线粒体消除促进代谢重编程以增加糖酵解来实现)在Rab32/38双敲除巨噬细胞中显著降低。因此,微自噬在巨噬细胞的生理调节中发挥作用。
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