학술논문
MIROs and DRP1 drive mitochondrial-derived vesicle biogenesis and promote quality control
Document Type
Report
Author
Source
Nature Cell Biology. December 2021, Vol. 23 Issue 12, p1271, 16 p.
Subject
Language
English
ISSN
1465-7392
Abstract
Author(s): Tim König [sup.1] , Hendrik Nolte [sup.2] , Mari J. Aaltonen [sup.1] , Takashi Tatsuta [sup.2] , Michiel Krols [sup.1] , Thomas Stroh [sup.1] , Thomas Langer [sup.2] [sup.3] [...]
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.sup.+ 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. By characterizing the composition of mitochondrial-derived vesicles (MDVs), König 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.sup.+ 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. By characterizing the composition of mitochondrial-derived vesicles (MDVs), König 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.