Evidence that mitochondria in macrophages are destroyed by microautophagy

Shiou-Ling Lu, Siyu Chen, Kazuya Noda, Yangjie Li, Chao-Yuan Tsai, Hiroko Omori, Yumiko Kato, Zidi Zhang, Bohan Chen, Kanako Tokuda, Tongxin Zheng, Masahiro Wakita, Eiji Hara, Mitsunori Fukuda, Yoh Wada, Eiji Morita, Narikazu Uzawa, Shinya Murakami and Takeshi Noda ()
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Shiou-Ling Lu: The University of Osaka
Siyu Chen: The University of Osaka
Kazuya Noda: The University of Osaka
Yangjie Li: The University of Osaka
Chao-Yuan Tsai: The University of Osaka
Hiroko Omori: The University of Osaka
Yumiko Kato: The University of Osaka
Zidi Zhang: The University of Osaka
Bohan Chen: The University of Osaka
Kanako Tokuda: The University of Osaka
Tongxin Zheng: The University of Osaka
Masahiro Wakita: The University of Osaka
Eiji Hara: The University of Osaka
Mitsunori Fukuda: Tohoku University
Yoh Wada: The University of Osaka
Eiji Morita: Hirosaki University
Narikazu Uzawa: The University of Osaka
Shinya Murakami: The University of Osaka
Takeshi Noda: The University of Osaka

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63531-x

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