COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome

Strien, Joeri van; Guerrero–Castillo, Sergio; Chatzispyrou, Iliana A.; Houtkooper, Riekelt H.; Brandt, Ulrich; Huynen, Martijn A.

doi:10.1101/411660

Cited by 6 publications

(12 citation statements)

References 40 publications

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“…However, LETM1 showed only a small fraction at this high molecular weight, suggesting a potentially dynamic/weak interaction. PHB and PHB2 steady-state levels were previously reported to be increased in TAZ1 mutants (Van Strien et al, 2019). Another CF-MS study (Stepanova et al, 2019), performed in neonate brain mitochondria under normal and succinate-supplemented conditions (which promotes reverse electron transfer/ROS formation), showed that only a small fraction of ATAD3 and LETM1 fractionate as a very large complex in either condition (Figures S5D and S5E).…”

Section: Atad3a Interacts With Letm1mentioning

confidence: 75%

“…Another database of interest was published by the Huynen Lab and included CF-MS of fibroblast samples of four patients with Barth syndrome, which have different mutations in the Tafazzin gene (Van Strien et al, 2019). Tafazzin gene product (TAZ1) remodels newly synthesized cardiolipin (CL), functioning as a monolysocardiolipin (MLCL) transacylase.…”

Section: Atad3a Interacts With Letm1mentioning

confidence: 99%

“…Data mining CF-MS was analyzed at https://fosterlab.github.io/CF-MS-analysis. Analysis of Tafazzin mutant samples was done using Supplementary figure S3 of reference (Van Strien et al, 2019). Analysis of neonate brain samples was done using Supplementary table S1 of reference (Stepanova et al, 2019).…”

Section: Periodicity Analysismentioning

confidence: 99%

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ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly

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Section: Atad3a Interacts With Letm1mentioning

confidence: 75%

Section: Atad3a Interacts With Letm1mentioning

confidence: 99%

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ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly

et al. 2021

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“…To account for experimental variations, we applied the COPAL tool (Van Strien et al , 2019) to align protein migration profiles and correct for differences in protein abundance from gel‐loading variations based on the total abundance of all detected MitoCarta 2.0 proteins (Dataset EV2). The aligned datasets contained 67 slices for each profile covering a mass range of approximately 20–3,300 kDa for membrane‐bound and 25–4,000 kDa for soluble proteins (Appendix Fig S1).…”

Section: Resultsmentioning

confidence: 99%

Ablation of mitochondrial DNA results in widespread remodeling of the mitochondrial complexome

et al. 2021

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So-called q0 cells lack mitochondrial DNA and are therefore incapable of aerobic ATP synthesis. How cells adapt to survive ablation of oxidative phosphorylation remains poorly understood. Complexome profiling analysis of q0 cells covered 1,002 mitochondrial proteins and revealed changes in abundance and organization of numerous multiprotein complexes including previously not described assemblies. Beyond multiple subassemblies of complexes that would normally contain components encoded by mitochondrial DNA, we observed widespread reorganization of the complexome. This included distinct changes in the expression pattern of adenine nucleotide carrier isoforms, other mitochondrial transporters, and components of the protein import machinery. Remarkably, ablation of mitochondrial DNA hardly affected the complexes organizing cristae junctions indicating that the altered cristae morphology in q0 mitochondria predominantly resulted from the loss of complex V dimers required to impose narrow curvatures to the inner membrane. Our data provide a comprehensive resource for in-depth analysis of remodeling of the mitochondrial complexome in response to respiratory deficiency.

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“…In baker's yeast, CL was required for the association of Mic27 with one of the two MICOS subcomplexes [66], as well as for stabilization of Mic10 oligomers [67], demonstrating that CL plays a role in the assembly and integrity of the MICOS complex. Moreover, OPA1, the MICOS complex, and the prohibitin complex were significantly affected in BTHS mitochondria, further supporting complex interplay between different cristae-shaping factors [68,69]. CL promotes the supramolecular organization of F 1 F o ATP synthase as dimers and oligomers [60].…”

Section: Emerging Roles Of Cardiolipin In Cristae Remodelingmentioning

confidence: 74%

Cristae Membrane Dynamics – A Paradigm Change

Kondadi

Anand

Reichert

2020

Trends in Cell Biology

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Mitochondria are dynamic organelles that have essential metabolic and regulatory functions. Earlier studies using electron microscopy (EM) revealed an immense diversity in the architecture of cristaeinfoldings of the mitochondrial inner membrane (IM)in different cells, tissues, bioenergetic and metabolic conditions, and during apoptosis. However, cristae were considered to be largely static entities. Recently, advanced super-resolution techniques have revealed that cristae are independent bioenergetic units that are highly dynamic and remodel on a timescale of seconds. These advances, coupled with mechanistic and structural studies on key molecular players, such as the MICOS (mitochondrial contact site and cristae organizing system) complex and the dynamin-like GTPase OPA1, have changed our view on mitochondria in a fundamental way. We summarize these recent findings and discuss their functional implications. The Changing Paradigm of Mitochondrial IM Structure and Dynamics Mitochondria are double-membrane-enclosed organelles of endosymbiotic origin that harbor an outer membrane (OM) and an inner membrane (IM). The immense diversity of mitochondrial ultrastructures was elucidated by electron microscopy (EM) over recent decades, and various models of cristae organization have been put forward [1]. The use of 3D electron tomography (ET) in the 1990s to decipher cristae structure by Terry Frey and Carmen Mannella led to seminal contributions that mark a shift in our view on cristae organization [2-4]. Cristae were no longer seen as extended, broad infoldings of the IM but instead were connected to the inner boundary membrane (IBM; see Glossary) by pore-or slit-like structures called crista junctions (CJs) (Box 1). CJs were proposed to act as diffusion barriers for membrane and soluble proteins, metabolites, and even protons [4,5]. Later studies confirmed that the IM is indeed subcompartmentalized [6-8]. Despite these advances and the conception that cristae are variable in structure, cristae were considered to be static under a particular physiological condition. This view was certainly biased because mitochondrial ultrastructure was studied using EM at high spatial resolution, although in fixed sample specimens. The static nature of cristae was propagated in textbooks for the past 60 years. In the 1960s, Charles Hackenbrock observed that addition of ADP could reversibly change the IM connectivity coupled with changes in mitochondrial matrix volume in isolated rat liver mitochondria [9,10], and this was corroborated using 3D ET experiments almost three decades later [3,5,11]. The latter studies also led to the proposal that cristae membrane (CM) reorganization might involve membrane fusion and fission events [5]. In addition, induction of apoptosis was accompanied by changes in the IM shape, connectivity, and matrix volume [12], which strongly suggested that cristae can dynamically change their structure. Hence, there were clear indications that CM remodeling can be induced by altered physiological conditions. The us...

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COmplexome Profiling ALignment (COPAL) reveals remodeling of mitochondrial protein complexes in Barth syndrome

Cited by 6 publications

References 40 publications

ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly

ATAD3A has a scaffolding role regulating mitochondria inner membrane structure and protein assembly

Ablation of mitochondrial DNA results in widespread remodeling of the mitochondrial complexome

Cristae Membrane Dynamics – A Paradigm Change

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