Protein Localization at Mitochondria-ER Contact Sites in Basal and Stress Conditions

Ilacqua, Nicolò; Sánchez-Álvarez, Miguel; Bachmann, Magdalena; Costiniti, Veronica; Pozo, Miguel Á. del; Giacomello, Marta

doi:10.3389/fcell.2017.00107

Cited by 20 publications

(16 citation statements)

References 173 publications

(206 reference statements)

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“…It is worth noting that the upregulation of IP3R might be a direct result of altered ER-associated degradation (ERAD) at ERMCS 55 . IP3R levels are controlled by ubiquitination, and the recent identification of the E3-ubiquitin ligase, Gp78, and other ERAD-associated proteins at ERMCS suggests that loss of ERMCS might affect the ubiquitination and subsequent proteasomal degradation of IP3R 51,56 . Our results suggest that this regulatory mechanism may be controlled by the levels or activity of Miro proteins although further studies are needed to uncover the molecular targets of Miro regulation.…”

Section: Discussionmentioning

confidence: 99%

Miro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery

et al. 2019

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Mitochondrial Rho (Miro) GTPases localize to the outer mitochondrial membrane and are essential machinery for the regulated trafficking of mitochondria to defined subcellular locations. However, their sub-mitochondrial localization and relationship with other critical mitochondrial complexes remains poorly understood. Here, using super-resolution fluorescence microscopy, we report that Miro proteins form nanometer-sized clusters along the mitochondrial outer membrane in association with the Mitochondrial Contact Site and Cristae Organizing System (MICOS). Using knockout mouse embryonic fibroblasts we show that Miro1 and Miro2 are required for normal mitochondrial cristae architecture and Endoplasmic Reticulum-Mitochondria Contacts Sites (ERMCS). Further, we show that Miro couples MICOS to TRAK motor protein adaptors to ensure the concerted transport of the two mitochondrial membranes and the correct distribution of cristae on the mitochondrial membrane. The Miro nanoscale organization, association with MICOS complex and regulation of ERMCS reveal new levels of control of the Miro GTPases on mitochondrial functionality.

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Section: Discussionmentioning

confidence: 99%

Miro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery

et al. 2019

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“…5e, f). Interestingly, several proteins (8 out of 27) also have literature connections to mitochondria-ER contact sites, which previous studies have linked to protein translation [44][45][46] ( Supplementary Fig. 5c).…”

Section: Discovery Of Rbps At the Outer Mitochondrial Membrane By Apementioning

confidence: 76%

Functional proximity mapping of RNA binding proteins uncovers a mitochondrial mRNA anchor that promotes stress recovery

Qin

Myers

Carey

et al. 2020

Preprint

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Proximity labeling (PL) with genetically-targeted promiscuous enzymes has emerged as a powerful tool for unbiased proteome discovery. By combining the spatiotemporal specificity of PL with methods for functional protein enrichment, it should be possible to map specific protein subclasses within distinct compartments of living cells. Here we demonstrate this capability for RNA binding proteins (RBPs), by combining peroxidase-based PL with organic-aqueous phase separation of crosslinked protein-RNA complexes (“APEX-PS”). We validated APEX-PS by mapping nuclear RBPs, then applied it to uncover the RBPomes of two unpurifiable subcompartments - the nucleolus and the outer mitochondrial membrane (OMM). At the OMM, we discovered the RBP SYNJ2BP, which retains specific nuclear-encoded mitochondrial mRNAs during translation stress, to promote their local translation and import of protein products into the mitochondrion during stress recovery. APEX-PS is a versatile tool for compartment-specific RBP discovery and expands the scope of PL to functional protein mapping.

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“…It is worth noting that the upregulation of IP3R might be a direct result of altered ER-associated degradation (ERAD) at ERMCS 76 . IP3R levels are controlled by ubiquitination and the recent identification of the E3-ubiquitin ligase, Gp78, and other ERAD associated proteins at ERMCS suggests that loss of ERMCS might affect the ubiquitination and subsequent proteasomal degradation of IP3R 41,77 . Our results suggest that this regulatory mechanism may be controlled by the levels or activity of Miro proteins although further studies are needed to uncover the molecular targets of Miro regulation.…”

Section: Discussionmentioning

confidence: 99%

Dual role of Miro protein clusters in mitochondrial cristae organisation and ER-Mitochondria Contact Sites

Modi

Lopez-Deomenech

Halff

et al. 2019

Preprint

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Mitochondrial Rho (Miro) GTPases localize to the outer mitochondrial membrane and are essential machinery for the regulated trafficking of mitochondria to defined subcellular locations. However, their sub-mitochondrial localization and relationship with other critical mitochondrial complexes remains poorly understood. Here, using super-resolution fluorescence microscopy, we report that Miro proteins form nanometer-sized clusters along the mitochondrial outer membrane in association with the Mitochondrial Contact Site and Cristae Organizing System (MICOS). Using knockout mouse embryonic fibroblasts (MEF) we show that Miro1 and Miro2 are required for normal mitochondrial cristae architecture and endoplasmic reticulum-mitochondria contacts sites (ERMCS). Further, we show that Miro couples MICOS to TRAK motor protein adaptors to ensure the concerted transport of the two mitochondrial membranes and the correct distribution of cristae on the mitochondrial membrane. The Miro nanoscale organization, association with MICOS complex and regulation of ERMCS reveal new levels of control of the Miro GTPases on mitochondrial functionality.

show abstract

Protein Localization at Mitochondria-ER Contact Sites in Basal and Stress Conditions

Cited by 20 publications

References 173 publications

Miro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery

Miro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery

Functional proximity mapping of RNA binding proteins uncovers a mitochondrial mRNA anchor that promotes stress recovery

Dual role of Miro protein clusters in mitochondrial cristae organisation and ER-Mitochondria Contact Sites

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