scholarly journals Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and Function by Impacting the Mitochondrial Protein Synthesis Machinery

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2147
Author(s):  
Bruno Seitaj ◽  
Felicia Maull ◽  
Li Zhang ◽  
Verena Wüllner ◽  
Christina Wolf ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Synthesis ◽  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Structure ◽  
Protein Synthesis Machinery ◽  
Atp Generation ◽  
And Function

The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson’s disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5-knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5-knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis.

scholarly journals Mdm38 is a 14-3-3-Like Receptor and Associates with the Protein Synthesis Machinery at the Inner Mitochondrial Membrane

Traffic ◽  
2011 ◽  
Vol 12 (10) ◽  
pp. 1457-1466 ◽  
Author(s):  
Domenico Lupo ◽  
Christine Vollmer ◽  
Markus Deckers ◽  
David U. Mick ◽  
Ivo Tews ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Membrane ◽  
Inner Mitochondrial Membrane ◽  
Protein Synthesis Machinery

scholarly journals The T. brucei TRM5 methyltransferase plays an essential role in mitochondrial protein synthesis and function

RNA ◽  
2013 ◽  
Vol 19 (5) ◽  
pp. 649-658 ◽  
Author(s):  
Z. Paris ◽  
E. Horakova ◽  
M. A. T. Rubio ◽  
P. Sample ◽  
I. M. C. Fleming ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Essential Role ◽  
Mitochondrial Protein ◽  
Mitochondrial Protein Synthesis ◽  
And Function

scholarly journals High resolution imaging of nascent mitochondrial protein synthesis in cultured human cells

2020 ◽  
Author(s):  
Matthew Zorkau ◽  
Christin A Albus ◽  
Rolando Berlinguer-Palmini ◽  
Zofia MA Chrzanowska-Lightowlers ◽  
Robert N. Lightowlers
Keyword(s):  
Protein Synthesis ◽  
Outer Membrane ◽  
Mitochondrial Protein ◽  
Human Cells ◽  
Mitochondrial Rna ◽  
Mitochondrial Protein Synthesis ◽  
Inner Mitochondrial Membrane ◽  
Rna Granules ◽  
Cultured Human Cells ◽  
Boundary Membrane

AbstractHuman mitochondria contain their own genome, mtDNA, that is expressed in the mitochondrial matrix. This genome encodes thirteen vital polypeptides that are components of the multi-subunit complexes that couple oxidative phosphorylation (OXPHOS). The inner mitochondrial membrane that houses these complexes comprises the inner boundary membrane that runs parallel to the outer membrane, infoldings that form the cristae membranes, and the cristae junctions that separate the two. It is in these cristae membranes that the OXPHOS complexes have been shown to reside in various species. The majority of the OXPHOS subunits are nuclear-encoded and must therefore be imported from the cytosol through the outer membrane at contact sites with the inner boundary membrane. As the mitochondrially-encoded components are also integral members of these complexes, where does nascent protein synthesis occur? Transcription, mRNA processing, maturation and at least part of the mitoribosome assembly process occur at the nucleoid and the spatially juxtaposed mitochondrial RNA granules, is protein synthesis also performed at the RNA granules close to these entities, or does it occur distal to these sites ? We have adapted a click chemistry based method, coupled with STED nanoscopy to address these questions. We report that in human cells in culture, within the limits of our methodology, the majority of mitochondrial protein synthesis occurs at the cristae membranes and is spatially separated from the sites of RNA processing and maturation.

scholarly journals Studies on mitochondrial structure and function in Physarum polycephalum. V. Behaviour of mitochondrial nucleoids throughout mitochondrial division cycle.

1977 ◽  
Vol 72 (3) ◽  
pp. 687-694 ◽  
Author(s):  
T Kuroiwa ◽  
S Kawano ◽  
M Hizume
Keyword(s):  
Physarum Polycephalum ◽  
Mitochondrial Membrane ◽  
Light And Electron Microscopy ◽  
Structure And Function ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Division ◽  
Mitochondrial Structure ◽  
Mitochondrial Nucleoids ◽  
And Function ◽  
Narrow Bridge

The fine structure of mitochondria and mitochondrial nucleoids in exponentially growing Physarum polycephalum was studied at various periods throughout the mitochondrial division cycle by light and electron microscopy. The mitochondrial nucleoid elongates lingitudinally while the mitochondrion increases in size. When the nucleoid reaches a length of approximately 1.5 mum the mitochondrial membrane invaginates at the center of the mitochondrion and separates the mitochondrial contents. However, the nucleoid does not divide even when the mitochondrial sections are connected by a very narrow bridge. Just before division of the mitochondrion, the nucleoid divides by constriction of the limiting membrane of the dividing mitochondrion. After division, one end of the nucleoid appears to be associated with the inner mitochondrial membrane. The nucleoid then again becomes situated in the center of the mitochondrion before repeating these same processes.

scholarly journals MICU1 regulates mitochondrial cristae structure and function independent of the mitochondrial calcium uniporter channel

2019 ◽  
Author(s):  
Dhanendra Tomar ◽  
Manfred Thomas ◽  
Joanne F. Garbincius ◽  
Devin W. Kolmetzky ◽  
Oniel Salik ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Mitochondrial Protein ◽  
Coiled Coil ◽  
Membrane Dynamics ◽  
Size Exclusion ◽  
Mitochondrial Calcium ◽  
Cellular Functions ◽  
Inner Mitochondrial Membrane ◽  
Cytochrome C Release ◽  
And Function

AbstractMICU1 is an EF-hand-containing mitochondrial protein that is essential for gating of the mitochondrial Ca2+ uniporter channel (mtCU) and is reported to interact directly with the pore-forming subunit, MCU and scaffold EMRE. However, using size-exclusion proteomics, we found that MICU1 exists in mitochondrial complexes lacking MCU. This suggests that MICU1 may have additional cellular functions independent of regulating mitochondrial Ca2+ uptake. To discern mtCU-independent MICU1 functions, we employed a proteomic discovery approach using BioID2-mediated proximity-based (<10nm) biotinylation and subsequent LC-MS detection. The expression of a MICU1-BioID2 fusion protein in MICU1-/- and MCU-/- cells allowed the identification of total vs. mtCU-independent MICU1 interactors. Bioinformatics identified the Mitochondrial Contact Site and Cristae Organizing System (MICOS) components MIC60 (encoded by the IMMT gene) and Coiled-coil-helix-coiled-coil helix domain containing 2 (CHCHD2) as novel MICU1 interactors, independent of the mtCU. We demonstrate that MICU1 is essential for proper proteomic organization of the MICOS complex and that MICU1 ablation results in altered cristae organization and mitochondrial ultrastructure. We hypothesize that MICU1 serves as a MICOS calcium sensor, since perturbing MICU1 is sufficient to modulate cytochrome c release independent of mitochondrial Ca2+ uptake across the inner mitochondrial membrane (IMM). Here, we provide the first experimental evidence suggesting that MICU1 regulates cellular functions independent of mitochondrial calcium uptake and may serve as a critical mediator of Ca2+-dependent signaling to modulate mitochondrial membrane dynamics and cristae organization.

Collection of Mitochondrial tRNA Sequences and Anticodon Identification for Acheta domesticus

2019 ◽  
Vol 967 ◽  
pp. 65-70
Author(s):  
Yash Munnalal Gupta ◽  
Kittisak Buddhachat ◽  
Surin Peyachoknagul ◽  
Somjit Homchan
Keyword(s):  
Protein Synthesis ◽  
Related Species ◽  
Mitochondrial Protein ◽  
Acheta Domesticus ◽  
Synthesis Process ◽  
Trna Genes ◽  
Mitochondrial Protein Synthesis ◽  
Mitochondrial Trna ◽  
Protein Synthesis Machinery ◽  
Codon Use

The mitochondria are organelles found within eukaryotic cell, possess own small circular DNA (mtDNA) apart from the most of DNA found in cell nucleus. The transcription and translation of mtDNA requires tRNA that often encoded by mtDNA itself. The mtDNA evolves faster than genomic DNA primary due to mitochondrial dysfunction and pathogenesis. The genes of mitochondria tRNA (mt tRNA) are prone to mutate that links to mitochondrial activity and protein synthesis machinery. It is important to understand the codon use by mt tRNA for Acheta domesticus to understand evolutionary relationship within closely related species and mitochondrial protein synthesis machinery. The present study uses the High throughput RNA sequencing data to identify mt tRNA genes using to examine the codon use for mitochondrial protein synthesis process. The conservative property of tRNA secondary structure assisted identified and confirmed anchored tRNA sequences with respective amino acid anticodon according to genetic code for tRNA in mtDNA. This study provides mt tRNA sequences to understand evolution of mitochondrial tRNA of Acheta domesticus with other related species to establish phylogeny. Moreover, mt tRNAs are the exons that provides partial sequences for mitochondria DNA. The novel approach for tRNA identification will guide other studies for PCR free in silico analysis.

scholarly journals Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 369 ◽  
Author(s):  
Kristýna Čunátová ◽  
David Pajuelo Reguera ◽  
Marek Vrbacký ◽  
Erika Fernández-Vizarra ◽  
Shujing Ding ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Proteins ◽  
Mitochondrial Protein ◽  
Metabolic Labeling ◽  
Mitochondrial Protein Synthesis ◽  
Cytochrome Bc1 Complex ◽  
Inner Mitochondrial Membrane ◽  
True Nature ◽  
Knock Out ◽  
Ideal System

The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependency of individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV) or cytochrome bc1 complex (cIII) deficiencies affect the level of fully assembled NADH dehydrogenase (cI) in monomeric as well as supercomplex forms. It was hypothesized that cI is affected at the level of enzyme assembly as well as at the level of cI stability and maintenance. However, the true nature of interdependency between cI and cIV is not fully understood yet. We used a HEK293 cellular model where the COX4 subunit was completely knocked out, serving as an ideal system to study interdependency of cI and cIV, as early phases of cIV assembly process were disrupted. Total absence of cIV was accompanied by profound deficiency of cI, documented by decrease in the levels of cI subunits and significantly reduced amount of assembled cI. Supercomplexes assembled from cI, cIII, and cIV were missing in COX4I1 knock-out (KO) due to loss of cIV and decrease in cI amount. Pulse-chase metabolic labeling of mitochondrial DNA (mtDNA)-encoded proteins uncovered a decrease in the translation of cIV and cI subunits. Moreover, partial impairment of mitochondrial protein synthesis correlated with decreased content of mitochondrial ribosomal proteins. In addition, complexome profiling revealed accumulation of cI assembly intermediates, indicating that cI biogenesis, rather than stability, was affected. We propose that attenuation of mitochondrial protein synthesis caused by cIV deficiency represents one of the mechanisms, which may impair biogenesis of cI.

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