Evidence that mitochondria in macrophages are destroyed by microautophagy

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

doi:https://doi.org/10.1038/s41467-025-63531-x

Evidence that mitochondria in macrophages are destroyed by microautophagy

Lu, Shiou Ling; Chen, Siyu; Noda, Kazuya et al.

Nature Communications, 2025, 16, 8123

Number of Access:565（2026-04-04 20:43 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/103500

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Title	Evidence that mitochondria in macrophages are destroyed by microautophagy
Creator	NRID 1000080830083 1000080830083 researchmap permalink sally711017 sally711017 Scopus Author ID 39863311300 39863311300 CreatorName Lu, Shiou Ling
	CreatorName Chen, Siyu
	CreatorName Noda, Kazuya
	CreatorName Li, Yangjie
	NRID 1000010727001 1000010727001 researchmap permalink chytsai chytsai CreatorName Tsai, Chao Yuan
	CreatorName Omori, Hiroko
	CreatorName Kato, Yumiko
	CreatorName Zhang, Zidi
	CreatorName Chen, Bohan
	CreatorName Tokuda, Kanako
	CreatorName Zheng, Tongxin
	NRID 1000070794668 1000070794668 researchmap permalink m.wakita m.wakita Scopus Author ID 57189681926 57189681926 CreatorName Wakita, Masahiro
	NRID 1000080263268 1000080263268 ORCID 0000-0001-7821-3960 0000-0001-7821-3960 researchmap permalink read0108962 read0108962 Scopus Author ID 7004944434 7004944434 CreatorName Hara, Eiji
	NRID 1000050311361 1000050311361 CreatorName Fukuda, Mitsunori
	NRID 1000050212329 1000050212329 ORCID 0000-0002-7783-7680 0000-0002-7783-7680 researchmap permalink read0046305 read0046305 Scopus Author ID 7403330464 7403330464 CreatorName Wada, Yoh
	NRID 1000070344653 1000070344653 CreatorName Morita, Eiji
	NRID 1000030345285 1000030345285 ORCID 0000-0001-5390-6875 0000-0001-5390-6875 researchmap permalink read0212957 read0212957 Scopus Author ID 6603144046 6603144046 CreatorName Uzawa, Narikazu
	NRID 1000070239490 1000070239490 ORCID 0000-0002-5230-452X 0000-0002-5230-452X researchmap permalink Shinya_Murakami Shinya_Murakami Scopus Author ID 7403706017 7403706017 CreatorName Murakami, Shinya
	NRID 1000000290908 1000000290908 ORCID 0000-0003-3581-7961 0000-0003-3581-7961 researchmap permalink takenoda takenoda Scopus Author ID 7402500250 7402500250 CreatorName Noda, Takeshi
Description	Lu S.L., Chen S., Noda K., et al. Evidence that mitochondria in macrophages are destroyed by microautophagy. Nature Communications 16, 8123 (2025); https://doi.org/10.1038/s41467-025-63531-x.
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.
Publisher	Nature Research
Source Title	Nature Communications
Volume (Issue)	16
Page	8123
Date of Issued	2025-08-30
Language	English
Handle URL	https://hdl.handle.net/11094/103500
eISSN	20411723
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41467-025-63531-x
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Nature Communications. 2025, 16, p. 8123
DC.title	Evidence that mitochondria in macrophages are destroyed by microautophagy
DC.creator	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
DC.publisher	Nature Research
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-08-30
DC.identifier	https://doi.org/10.1038/s41467-025-63531-x
DC.description	Lu S.L., Chen S., Noda K., et al. Evidence that mitochondria in macrophages are destroyed by microautophagy. Nature Communications 16, 8123 (2025); https://doi.org/10.1038/s41467-025-63531-x.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	103500
citation_title	Evidence that mitochondria in macrophages are destroyed by microautophagy
citation_author	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
citation_publisher	Nature Research
citation_language	English
citation_date	2025-08-30
citation_journal_title	Nature Communications
citation_volume	16
citation_firstpage	8123
citation_doi	https://doi.org/10.1038/s41467-025-63531-x
citation_public_url	https://hdl.handle.net/11094/103500

Evidence that mitochondria in macrophages are destroyed by microautophagy

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