Building a complex complex: Assembly of mitochondrial respiratory chain complex I

Formosa, Luke E.; Dibley, Marris G.; Stroud, David A.; Ryan, Michael

doi:10.1016/j.semcdb.2017.08.011

Cited by 167 publications

(164 citation statements)

References 94 publications

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“…1C, this was indeed the case: MTRF1L, a mitochondrial translation termination factor, specifically enriched MRPL53 and MRPL10, two mitochondrial ribosomal proteins present at the L7/L12 stalk, a site responsible for the recruitment of mitochondrial translation factors (Brown et al, 2014). Proximity interactors of ACAD9, a mitochondrial Complex I assembly factor, which is part of the MCIA complex responsible for ND2 module assembly (Formosa et al, 2018) were enriched for two other proteins of this complex (NDUFAF1 and ESCIT), as well as for ND2 protein itself and COA1, recently shown to be responsible for the translation of ND2 (Wang et al, 2020). Lastly, LRPPRC very strongly enriched SLIRP, with which it is known to form a stable complex (Sasarman et al, 2010) that is necessary for stabilization and polyadenylation of mitochondrial mRNAs (Chujo et al, 2012;Ruzzenente et al, 2012).…”

Section: Definition Of the Mitochondrial Matrix And Ims Bioid Environmentioning

confidence: 89%

A high-density human mitochondrial proximity interaction network

Antonická

Lin

Janer

et al. 2020

Preprint

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We used BioID, a proximity-dependent biotinylation assay, to interrogate 100 mitochondrial baits from all mitochondrial sub-compartments to create a high resolution human mitochondrial proximity interaction network. We identified 1465 proteins, producing 15626 unique high confidence proximity interactions. Of these, 528 proteins were previously annotated as mitochondrial, nearly half of the mitochondrial proteome defined by Mitocarta 2.0. Bait-bait analysis showed a clear separation of mitochondrial compartments, and correlation analysis among preys across all baits allowed us to identify functional clusters involved in diverse mitochondrial functions, and to assign uncharacterized proteins to specific modules. We demonstrate that this analysis can assign isoforms of the same mitochondrial protein to different mitochondrial sub-compartments, and show that some proteins may have multiple cellular locations. Outer membrane baits showed specific proximity interactions with cytosolic proteins and proteins in other organellar membranes, suggesting specialization of proteins responsible for contact site formation between mitochondria and individual organelles. This proximity network will be a valuable resource for exploring the biology of uncharacterized mitochondrial proteins, the interactions of mitochondria with other cellular organelles, and will provide a framework to interpret alterations in sub-mitochondrial environments associated with mitochondrial disease. Bullet points• We created a high resolution human mitochondrial protein proximity map using BioID• Bait-bait analysis showed that the map has sub-compartment resolution and correlation analysis of preys identified functional clusters and assigned proteins to specific modules• We identified isoforms of matrix and IMS proteins with multiple cellular localizations and an endonuclease that localizes to both the matrix and the OMM • OMM baits showed specific interactions with non-mitochondrial proteins reflecting organellar contact sites and protein dual localization 2013). Mitochondrial diseases due to deficiencies in the oxidative phosphorylation machinery are amongst the most common inherited metabolic disorders (Frazier et al., 2019;Nunnari and Suomalainen, 2012). While nearly 300 causal genes have now been identified, the molecular basis for the extraordinary tissue specificity associated with these diseases remains an enduring mystery.Mitochondria are double-membraned organelles, whose ultrastructure has been investigated for decades. The outer membrane (OMM), which serves as a platform for molecules involved in the regulation of innate immunity and for regulation of apoptosis, is permeable to metabolites and small proteins, and it forms close contacts with the endoplasmic reticulum (ER) for the exchange of lipids and calcium (Csordas et al., 2018). The impermeable inner membrane (IMM) is composed of invaginations called cristae that contain the complexes of the oxidative phosphorylation system. The intermembrane space (IMS) comprises both the space formed...

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Section: Definition Of the Mitochondrial Matrix And Ims Bioid Environmentioning

confidence: 89%

A high-density human mitochondrial proximity interaction network

Antonická

Lin

Janer

et al. 2020

Preprint

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“…It is responsible for oxidising NADH in the mitochondrial matrix, regenerating NAD + to sustain the TCA cycle and fatty acid oxidation, as well as contributing to the proton gradient across the inner membrane. Mammalian Complex I consists of 45 subunits including 7 encoded by mtDNA and 37 by nDNA, one of which is present twice in the complex [31,55,56]. While the high-resolution structures of the complete or nearcomplete Complexes III and IV were determined by X-ray crystallography in the 1990s, the sheer scale of Complex I necessitated a combination of X-ray crystallography, Cryo-EM and improved sample preparation techniques to reveal its high-resolution structure.…”

Section: Nadh:ubiquinone Oxidoreductase -Complex Imentioning

confidence: 99%

The road to the structure of the mitochondrial respiratory chain supercomplex

Caruana

Stroud

2020

Biochemical Society Transactions

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The four complexes of the mitochondrial respiratory chain are critical for ATP production in most eukaryotic cells. Structural characterisation of these complexes has been critical for understanding the mechanisms underpinning their function. The three proton-pumping complexes, Complexes I, III and IV associate to form stable supercomplexes or respirasomes, the most abundant form containing 80 subunits in mammals. Multiple functions have been proposed for the supercomplexes, including enhancing the diffusion of electron carriers, providing stability for the complexes and protection against reactive oxygen species. Although high-resolution structures for Complexes III and IV were determined by X-ray crystallography in the 1990s, the size of Complex I and the supercomplexes necessitated advances in sample preparation and the development of cryo-electron microscopy techniques. We now enjoy structures for these beautiful complexes isolated from multiple organisms and in multiple states and together they provide important insights into respiratory chain function and the role of the supercomplex. While we as non-structural biologists use these structures for interpreting our own functional data, we need to remind ourselves that they stand on the shoulders of a large body of previous structural studies, many of which are still appropriate for use in understanding our results. In this mini-review, we discuss the history of respiratory chain structural biology studies leading to the structures of the mammalian supercomplexes and beyond.

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“…In past years considerable advances have been made in defining the distinct steps of the assembly pathway of complex I. Briefly, complex I is assembled in a modular manner: building blocks or assembly intermediates comprising several subunits are formed and later assembled together into the holocomplex (Vartak et al, 2014;Subrahmanian et al, 2016;Guerrero-Castillo et al, 2017a;Formosa et al, 2018). When assembly is disturbed, for example when a subunit or assembly factor is missing, low levels of assembly intermediates accumulate (Meyer et al, 2011;Stroud et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The assembly pathway of complex I in Arabidopsis thaliana

et al. 2018

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Summary All present‐day mitochondria originate from a single endosymbiotic event that gave rise to the last eukaryotic common ancestor more than a billion years ago. However, to date, many aspects of mitochondrial evolution have remained unresolved. Comparative genomics and proteomics have revealed a complex evolutionary origin for many mitochondrial components. To understand the evolution of the respiratory chain, we have examined both the components and the mechanisms of the assembly pathway of complex I. Complex I represents the first enzyme in the respiratory chain, and complex I deficiencies have dramatic consequences in both animals and plants. The complex is located in the mitochondrial inner membrane and possesses two arms: one embedded in the inner membrane and one protruding in the matrix. Here, we describe the assembly pathway of complex I in the model plant Arabidopsis thaliana. Using a proteomics approach called complexome profiling, we have resolved the different steps in the assembly process in plants. We propose a model for the stepwise assembly of complex I, including every subunit. We then compare this pathway with the corresponding pathway in humans and find that complex I assembly in plants follows a different, and likely ancestral, pathway compared with the one in humans. We show that the main evolutionary changes in complex I structure and assembly in humans occurred at the level of the membrane arm, whereas the matrix arm remained rather conserved.

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Building a complex complex: Assembly of mitochondrial respiratory chain complex I

Cited by 167 publications

References 94 publications

A high-density human mitochondrial proximity interaction network

A high-density human mitochondrial proximity interaction network

The road to the structure of the mitochondrial respiratory chain supercomplex

The assembly pathway of complex I in Arabidopsis thaliana

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