Universität zu Köln

Koenig, Tim, Nolte, Hendrik, Aaltonen, Mari J. ORCID: 0000-0002-7333-9334, Tatsuta, Takashi, Krols, Michiel, Stroh, Thomas, Langer, Thomas and McBride, Heidi M. ORCID: 0000-0003-4666-2280 (2021). MIROs and DRP1 drive mitochondrial-derived vesicle biogenesis and promote quality control. Nat. Cell Biol., 23 (12). S. 1271 - 1305. BERLIN: NATURE PORTFOLIO. ISSN 1476-4679

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Abstract

By characterizing the composition of mitochondrial-derived vesicles (MDVs), Konig et al. define a MIRO1/2- and DRP1-dependent MDV biogenesis pathway and propose that MDVs maintain the mitochondrial proteome by shuttling assembled protein complexes to lysosomes. Mitochondrial-derived vesicles (MDVs) are implicated in diverse physiological processes-for example, mitochondrial quality control-and are linked to various neurodegenerative diseases. However, their specific cargo composition and complex molecular biogenesis are still unknown. Here we report the proteome and lipidome of steady-state TOMM20(+) MDVs. We identified 107 high-confidence MDV cargoes, which include all beta-barrel proteins and the TOM import complex. MDV cargoes are delivered as fully assembled complexes to lysosomes, thus representing a selective mitochondrial quality control mechanism for multi-subunit complexes, including the TOM machinery. Moreover, we define key biogenesis steps of phosphatidic acid-enriched MDVs starting with the MIRO1/2-dependent formation of thin membrane protrusions pulled along microtubule filaments, followed by MID49/MID51/MFF-dependent recruitment of the dynamin family GTPase DRP1 and finally DRP1-dependent scission. In summary, we define the function of MDVs in mitochondrial quality control and present a mechanistic model for global GTPase-driven MDV biogenesis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Koenig, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Aaltonen, Mari J. UNSPECIFIED orcid.org/0000-0002-7333-9334 UNSPECIFIED Tatsuta, Takashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Krols, Michiel UNSPECIFIED UNSPECIFIED UNSPECIFIED Stroh, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Langer, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED McBride, Heidi M. UNSPECIFIED orcid.org/0000-0003-4666-2280 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-578173
DOI:	10.1038/s41556-021-00798-4
Journal or Publication Title:	Nat. Cell Biol.
Volume:	23
Number:	12
Page Range:	S. 1271 - 1305
Date:	2021
Publisher:	NATURE PORTFOLIO
Place of Publication:	BERLIN
ISSN:	1476-4679
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language QUANTITATIVE-ANALYSIS; PHOSPHATIDIC-ACID; MITOPHAGY; TRANSPORT; PROTEINS; FISSION; PARKIN; CARGO; MICROTUBULE; PEROXISOMES Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57817