A High-Density Human Mitochondrial Proximity Interaction Network

Antonická, Hana; Lin, Zhen‐Yuan; Janer, Alexandre; Aaltonen, Mari J.; Weraarpachai, Woranontee; Gingras, Anne‐Claude; Shoubridge, Eric A.

doi:10.1016/j.cmet.2020.07.017

Cited by 150 publications

(154 citation statements)

References 99 publications

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“…An association of VPS13D with mitochondria is also supported by recent proximity-labelling based studies listing this protein among the hits retrieved with outer membrane protein baits (Hung et al, 2017;Liu et al, 2018;Antonicka et al, 2020).…”

Section: Discussionmentioning

confidence: 59%

VPS13D bridges the ER to Miro containing membranes

Guillén-Samander

Leonzino

Hanna

et al. 2020

Preprint

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Mitochondria, which are excluded from the secretory pathway, depend on lipid transport proteins for their lipid supply from the ER, where most lipids are synthesized. In yeast, the outer membrane GTPase Gem1 is an accessory factor of ERMES, an ER-mitochondria tethering complex that contains lipid transport domains and plays a function, partially redundant with VPS13, in lipid transfer between the two organelles. In metazoa, where VPS13, but not ERMES, is present, the Gem1 orthologue Miro has been linked to mitochondrial motility but not to lipid transport. Here we show that Miro recruits to mitochondria the lipid transport protein VPS13D which, like Miro, is an essential protein in mammals, and whose localization had remained elusive. We also show that VPS13D can tether mitochondria to the ER in a Miro- and VAP-dependent way. These findings reveal a so far missing link between function(s) of Gem1/Miro in yeast and higher eukaryotes, where Miro is a Parkin substrate, with potential implications for Parkinson’s disease pathogenesis.SummaryProtein-mediated ER-mitochondria lipid transfer is critical for eukaryotic cells. However, the underlying machinery is not well conserved. Guillén-Samander et al, show that Gem1/Miro is an evolutionary conserved link between the yeast ERMES complex and the mammalian lipid transfer protein VPS13D.

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Section: Discussionmentioning

confidence: 59%

VPS13D bridges the ER to Miro containing membranes

Guillén-Samander

Leonzino

Hanna

et al. 2020

Preprint

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“…To assess the accuracy of our sub-mitochondrial localizations, we compared our annotations to a recently published mitochondrial proximity interaction network ( 31 ). Considering all 11,569 bait–prey interactions between MitoCarta3.0 proteins, which covers nearly half of MitoCarta3.0 (527/1136 genes), we find that 98% of interactions are consistent with our annotated localizations.…”

Section: Mitocarta30mentioning

confidence: 99%

MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations

Rath

Sharma

Gupta

et al. 2020

Nucleic Acids Research

992

842

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The mammalian mitochondrial proteome is under dual genomic control, with 99% of proteins encoded by the nuclear genome and 13 originating from the mitochondrial DNA (mtDNA). We previously developed MitoCarta, a catalogue of over 1000 genes encoding the mammalian mitochondrial proteome. This catalogue was compiled using a Bayesian integration of multiple sequence features and experimental datasets, notably protein mass spectrometry of mitochondria isolated from fourteen murine tissues. Here, we introduce MitoCarta3.0. Beginning with the MitoCarta2.0 inventory, we performed manual review to remove 100 genes and introduce 78 additional genes, arriving at an updated inventory of 1136 human genes. We now include manually curated annotations of sub-mitochondrial localization (matrix, inner membrane, intermembrane space, outer membrane) as well as assignment to 149 hierarchical ‘MitoPathways’ spanning seven broad functional categories relevant to mitochondria. MitoCarta3.0, including sub-mitochondrial localization and MitoPathway annotations, is freely available at http://www.broadinstitute.org/mitocarta and should serve as a continued community resource for mitochondrial biology and medicine.

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“…Tagged at either terminus, ORF9B recovered a number of outer mitochondrial membrane proteins, including TOMM70, a mitochondrial import receptor subunit shown to associate with ORF9B in three other studies 6,7,32 , and whose binding can be recapitulated in vitro by purified proteins 32 . ORF9B also recovers many peptides for MAVS, a protein required for innate immune defense against viruses (reviewed in 33 ) that we previously studied in the context of a BioID map of mitochondrial organization 34 . This is consistent with a recently confirmed role of ORF9B in the regulation of innate immunity 35 .…”

Section: Nsp7 and Nsp8mentioning

confidence: 99%

“…Entry vectors for host cell proteins previously used as proximity-dependent biotinylation (BioID) subcellular markers were transferred into pSTV2-miniTurbo N-or C-termini vectors (the orientation was kept consistent with our previous study 20 ). MAVS entry vector was subcloned with a N-terminal tag as in 34 . The signal sequence from IgKV4-1 (MVLQTQVFISLLLWISGAYG) followed by an HA-tag (YPYDVPDY) and residues 617-675 from CD44 that contains a portion of the extracellular domain, and the transmembrane domain (residues 643-675) without a stop-codon were amplified using standard AttB1/2 gateway primers to generate an entry vector.…”

Section: Cloningmentioning

confidence: 99%

A SARS-CoV-2 – host proximity interactome

Samavarchi-Tehrani

Abdouni

Knight

et al. 2020

Preprint

Self Cite

131

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Viral replication is dependent on interactions between viral polypeptides and host proteins. Identifying virus-host protein interactions can thus uncover unique opportunities for interfering with the virus life cycle via novel drug compounds or drug repurposing. Importantly, many viral-host protein interactions take place at intracellular membranes and poorly soluble organelles, which are difficult to profile using classical biochemical purification approaches. Applying proximity-dependent biotinylation (BioID) with the fast-acting miniTurbo enzyme to 27 SARS-CoV-2 proteins in a lung adenocarcinoma cell line (A549), we detected 7810 proximity interactions (7382 of which are new for SARS-CoV-2) with 2242 host proteins (results available at covid19interactome.org). These results complement and dramatically expand upon recent affinity purification-based studies identifying stable host-virus protein complexes, and offer an unparalleled view of membrane-associated processes critical for viral production. Host cell organellar markers were also subjected to BioID in parallel, allowing us to propose modes of action for several viral proteins in the context of host proteome remodelling. In summary, our dataset identifies numerous high confidence proximity partners for SARS-CoV-2 viral proteins, and describes potential mechanisms for their effects on specific host cell functions.

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A High-Density Human Mitochondrial Proximity Interaction Network

Cited by 150 publications

References 99 publications

VPS13D bridges the ER to Miro containing membranes

VPS13D bridges the ER to Miro containing membranes

MitoCarta3.0: an updated mitochondrial proteome now with sub-organelle localization and pathway annotations

A SARS-CoV-2 – host proximity interactome

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