Evidence that mitochondria in macrophages are destroyed by microautophagy

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.

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Publication Details

Journal
Nature Communications
Published
2025-08-30
DOI
https://doi.org/10.1038/s41467-025-63531-x
Citations
5
Primary Topic
Autophagy in Disease and Therapy
Type
article
Field-Weighted Citation Impact
6.77

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article

Evidence that mitochondria in macrophages are destroyed by microautophagy

Shinya Murakami, Mitsunori Fukuda, Takeshi Noda, Eiji Morita et al.
5 citations
Nature Communications
Autophagy in Disease and Therapy
6.77
article

Evidence that mitochondria in macrophages are destroyed by microautophagy

Shinya Murakami, Mitsunori Fukuda, Takeshi Noda, Eiji Morita, Shiou-Ling Lu, Yoh Wada, Hiroko Omori, Narikazu Uzawa, Zi-di Zhang, B. Chen, Yangjie Li, Eiji Hara, Masahiro Wakita, Siyu Chen, Chao‐Yuan Tsai, Tianle Zheng, Yumiko Kato, K. Tokuda, Kazuya Noda
article en
5 citations

Abstract

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.

Nature CommunicationsVol. 16(1)
Hirosaki University (JP), Tohoku University (JP), Ube Frontier University (JP), Osaka City University (JP), Osaka Research Institute of Industrial Science and Technology (JP), Immune Regulation (United Kingdom) (GB), Osaka International Cancer Institute (JP), Osaka University of Pharmaceutical Sciences (JP), Osaka Dental University (JP), The University of Osaka (JP)
Hirose Foundation, Japan Society for the Promotion of Science
Zero hunger
Openalex Percentile: Top 3%
Autophagy in Disease and Therapy
6.77
DOIOpen Access PDFOpenAlex
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