Genomes and Genes
mitochondrial membrane transport proteins
Summary: Proteins involved in the transport of specific substances across the membranes of the MITOCHONDRIA.
- Mallilankaraman K, Cardenas C, Doonan P, Chandramoorthy H, Irrinki K, Golenár T, et al. MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism. Nat Cell Biol. 2012;14:1336-43 pubmed publisher..Thus, MCUR1 is a critical component of a mitochondrial uniporter channel complex required for mitochondrial Ca(2+) uptake and maintenance of normal cellular bioenergetics. ..
- Csordás G, Golenár T, Seifert E, Kamer K, Sancak Y, Perocchi F, et al. MICU1 controls both the threshold and cooperative activation of the mitochondrial Ca²? uniporter. Cell Metab. 2013;17:976-87 pubmed publisher..Collectively, the data indicate that MICU1 senses the [Ca(2+)]c to establish the uniporter's threshold and gain, thereby allowing mitochondria to properly decode different inputs. ..
- Vitoria I, Dalmau J, Ribes C, Rausell D, Garcia A, López Montiel J, et al. Citrin deficiency in a Romanian child living in Spain highlights the worldwide distribution of this defect and illustrates the value of nutritional therapy. Mol Genet Metab. 2013;110:181-3 pubmed publisher..An immediate response to a high-protein, lactose-free, low-carbohydrate formula was observed. Our report illustrates the need for awareness on citrin deficiency in Western countries. ..
- Wang X, Jian C, Zhang X, Huang Z, Xu J, Hou T, et al. Superoxide flashes: elemental events of mitochondrial ROS signaling in the heart. J Mol Cell Cardiol. 2012;52:940-8 pubmed publisher..Future investigation is warranted to uncover the cellular logic and molecular pathways of local dynamic mitoROS signaling in heart muscle cells and many other cell types...
- Weckbecker D, Longen S, Riemer J, Herrmann J. Atp23 biogenesis reveals a chaperone-like folding activity of Mia40 in the IMS of mitochondria. EMBO J. 2012;31:4348-58 pubmed publisher..Thus, Mia40 plays a much broader role in import and folding of polypeptides than previously expected and can serve as folding factor for proteins with complex disulphide patterns as well as for cysteine-free polypeptides. ..
- Mick D, Dennerlein S, Wiese H, Reinhold R, Pacheu Grau D, Lorenzi I, et al. MITRAC links mitochondrial protein translocation to respiratory-chain assembly and translational regulation. Cell. 2012;151:1528-41 pubmed publisher..We establish an unexpected molecular link between the TIM23 transport machinery and assembly of respiratory-chain complexes that regulate mitochondrial protein synthesis in response to their assembly state. ..
- Kojer K, Bien M, Gangel H, Morgan B, Dick T, Riemer J. Glutathione redox potential in the mitochondrial intermembrane space is linked to the cytosol and impacts the Mia40 redox state. EMBO J. 2012;31:3169-82 pubmed publisher..Taken together, we provide a comprehensive mechanistic picture of the IMS redox milieu and define the redox influences on Mia40 in living cells. ..
- Plovanich M, Bogorad R, Sancak Y, Kamer K, Strittmatter L, Li A, et al. MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling. PLoS ONE. 2013;8:e55785 pubmed publisher..The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel. ..
- Bragoszewski P, Gornicka A, Sztolsztener M, Chacinska A. The ubiquitin-proteasome system regulates mitochondrial intermembrane space proteins. Mol Cell Biol. 2013;33:2136-48 pubmed publisher..Thus, the ubiquitin-proteasome system plays an important role in determining the levels of proteins targeted to the intermembrane space of mitochondria. ..
- Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M, et al. Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci U S A. 2013;110:5887-92 pubmed publisher..Channel openings were inhibited by the ATP synthase inhibitor AMP-PNP (?-imino ATP, a nonhydrolyzable ATP analog) and Mg(2+)/ADP. These results indicate that the PTP forms from dimers of the ATP synthase. ..
- Durigon R, Wang Q, Ceh Pavia E, Grant C, Lu H. Cytosolic thioredoxin system facilitates the import of mitochondrial small Tim proteins. EMBO Rep. 2012;13:916-22 pubmed publisher..Here we provide the first evidence that the cytosolic thioredoxin system is required to maintain the IMS small Tim proteins in reduced forms and facilitate their mitochondrial import during respiratory growth. ..
- Banci L, Barbieri L, Luchinat E, Secci E. Visualization of redox-controlled protein fold in living cells. Chem Biol. 2013;20:747-52 pubmed publisher..Overexpressed cytoplasmic Mia40 is folded, and its folding state depends on the glutaredoxin 1 (Grx1) and thioredoxin 1 (Trx1) systems. Specifically, increased Grx1 levels keep most Mia40 unfolded, while Trx1 is less effective. ..
- Wrobel L, Trojanowska A, Sztolsztener M, Chacinska A. Mitochondrial protein import: Mia40 facilitates Tim22 translocation into the inner membrane of mitochondria. Mol Biol Cell. 2013;24:543-54 pubmed publisher..We propose that Mia40 not only is responsible for disulfide bond formation, but also assists the Tim22 protein in its integration into the inner membrane of mitochondria. ..
- Guo P, Ma J, Jiang Y, Wang S, Bao Z, Yu X, et al. Structure of yeast sulfhydryl oxidase erv1 reveals electron transfer of the disulfide relay system in the mitochondrial intermembrane space. J Biol Chem. 2012;287:34961-9 pubmed publisher..These findings provide structural insights into electron transfer from Mia40 via the shuttle domain of one subunit of Erv1 to the CTD of another Erv1 subunit...
- Vaseva A, Marchenko N, Ji K, Tsirka S, Holzmann S, Moll U. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012;149:1536-48 pubmed publisher..Our study identifies the mitochondrial p53-CypD axis as an important contributor to oxidative stress-induced necrosis and implicates this axis in stroke pathology. ..
- Sancak Y, Markhard A, Kitami T, Kovács Bogdán E, Kamer K, Udeshi N, et al. EMRE is an essential component of the mitochondrial calcium uniporter complex. Science. 2013;342:1379-82 pubmed publisher..EMRE was required for the interaction of MCU with MICU1 and MICU2. Hence, EMRE is essential for in vivo uniporter current and additionally bridges the calcium-sensing role of MICU1 and MICU2 with the calcium-conducting role of MCU. ..
- Böttinger L, Gornicka A, Czerwik T, Bragoszewski P, Loniewska Lwowska A, Schulze Specking A, et al. In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins. Mol Biol Cell. 2012;23:3957-69 pubmed publisher..Thus Mia40 in cooperation with Erv1 promotes the formation of two disulfide bonds in the substrate protein, ensuring the efficiency of oxidative folding in the intermembrane space of mitochondria. ..
- Spiller M, Ang S, Ceh Pavia E, Fisher K, Wang Q, Rigby S, et al. Identification and characterization of mitochondrial Mia40 as an iron-sulfur protein. Biochem J. 2013;455:27-35 pubmed publisher..Thus we conclude that Mia40 is a novel Fe-S protein with a new cluster-binding motif (CPC), and apart from the thiol oxidoreductase activity, Mia40 may have another important, as yet undefined, function in cells. ..
- Ryu S, Choi K, Park J, Park Y, Kim S, Choi C. Mitofusin 1 inhibits an apoptosis-associated amino-terminal conformational change in Bax, but not its mitochondrial translocation, in a GTPase-dependent manner. Cancer Lett. 2012;323:62-8 pubmed publisher..These results collectively suggest a role for Mfn1 in regulating the activation of Bax on the outer mitochondrial membrane in a GTPase-dependent manner. ..
- Ling X, Zhou Y, Li S, Yan B, Wen L. Modulation of mitochondrial permeability transition pore affects multidrug resistance in human hepatocellular carcinoma cells. Int J Biol Sci. 2010;6:773-83 pubmed..In conclusion, selective modulation of mPTP can affect MDR in human HCC cells. Therefore, activation of mPTP may provide a new strategy to sensitize cancer cells to chemotherapeutic drugs and to reverse the MDR in cancer cells. ..
- Hafner A, Dai J, Gomes A, Xiao C, Palmeira C, Rosenzweig A, et al. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY). 2010;2:914-23 pubmed
- Perocchi F, Gohil V, Girgis H, Bao X, McCombs J, Palmer A, et al. MICU1 encodes a mitochondrial EF hand protein required for Ca(2+) uptake. Nature. 2010;467:291-6 pubmed publisher..Its discovery may lead to the complete molecular characterization of mitochondrial calcium uptake pathways, and offers genetic strategies for understanding their contribution to normal physiology and disease. ..
- Elrod J, Wong R, Mishra S, Vagnozzi R, Sakthievel B, Goonasekera S, et al. Cyclophilin D controls mitochondrial pore-dependent Ca(2+) exchange, metabolic flexibility, and propensity for heart failure in mice. J Clin Invest. 2010;120:3680-7 pubmed publisher..These findings suggest that the MPTP maintains homeostatic mitochondrial Ca(2+) levels to match metabolism with alterations in myocardial workload, thereby suggesting a physiologic function for the MPTP...
- Loor G, Kondapalli J, Iwase H, Chandel N, Waypa G, Guzy R, et al. Mitochondrial oxidant stress triggers cell death in simulated ischemia-reperfusion. Biochim Biophys Acta. 2011;1813:1382-94 pubmed publisher..Therefore, mitochondrial apoptosis appears to represent a redundant death pathway in this model of simulated I/R. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. ..
- Gross D, Burgard C, Reddehase S, Leitch J, Culotta V, Hell K. Mitochondrial Ccs1 contains a structural disulfide bond crucial for the import of this unconventional substrate by the disulfide relay system. Mol Biol Cell. 2011;22:3758-67 pubmed publisher..Thus the disulfide relay system is able to form, in addition to double disulfide bonds in twin Cx(n)C motifs, single structural disulfide bonds in complex protein domains. ..
- Papic D, Krumpe K, Dukanovic J, Dimmer K, Rapaport D. Multispan mitochondrial outer membrane protein Ugo1 follows a unique Mim1-dependent import pathway. J Cell Biol. 2011;194:397-405 pubmed publisher..Collectively, these results suggest that Ugo1 is inserted into the MOM by a novel pathway in which Tom70 and Mim1 contribute to the efficiency and selectivity of the process. ..
- Tschopp F, Charrière F, Schneider A. In vivo study in Trypanosoma brucei links mitochondrial transfer RNA import to mitochondrial protein import. EMBO Rep. 2011;12:825-32 pubmed publisher..These findings, together with previous results in yeast and plants, suggest that the requirement for mitochondrial protein-import factors might be a conserved feature of mitochondrial tRNA import in all systems. ..
- Rimmer K, Foo J, Ng A, Petrie E, Shilling P, Perry A, et al. Recognition of mitochondrial targeting sequences by the import receptors Tom20 and Tom22. J Mol Biol. 2011;405:804-18 pubmed publisher..AtTom22, however, binds to AtTom20 at the same binding site as presequences, suggesting that this domain competes with the presequences of imported proteins, thereby enabling their progression along the import pathway. ..
- Di Lisa F, Carpi A, Giorgio V, Bernardi P. The mitochondrial permeability transition pore and cyclophilin D in cardioprotection. Biochim Biophys Acta. 2011;1813:1316-22 pubmed publisher..This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. ..
- Gebert N, Gebert M, Oeljeklaus S, von der Malsburg K, Stroud D, Kulawiak B, et al. Dual function of Sdh3 in the respiratory chain and TIM22 protein translocase of the mitochondrial inner membrane. Mol Cell. 2011;44:811-8 pubmed publisher..We conclude that the assembly of Sdh3 with different partner proteins, Sdh4 and Tim18, recruits it to two different mitochondrial membrane complexes with functions in bioenergetics and protein biogenesis, respectively. ..
- Hausenloy D, Boston Griffiths E, Yellon D. Cyclosporin A and cardioprotection: from investigative tool to therapeutic agent. Br J Pharmacol. 2012;165:1235-45 pubmed publisher..In this article, we review the intriguing role of CsA as a tool for investigating the mPTP as a target for cardioprotection and its potential role as a therapeutic agent for patients with IHD. ..
- Fu H, Zhang S, Wang X, Saheki T, Kobayashi K, Wang J. The mutation spectrum of the SLC25A13 gene in Chinese infants with intrahepatic cholestasis and aminoacidemia. J Gastroenterol. 2011;46:510-8 pubmed publisher..The SLC25A13 gene mutation is the most important cause of infantile intrahepatic cholestasis with various forms of aminoacidemia. ..
- Harner M, Neupert W, Deponte M. Lateral release of proteins from the TOM complex into the outer membrane of mitochondria. EMBO J. 2011;30:3232-41 pubmed publisher..Our results demonstrate that the TOM complex, depending on sequence determinants in the precursors, can act both as a protein conducting pore and as an insertase mediating lateral release into the outer membrane. ..
- Boengler K, Hilfiker Kleiner D, Heusch G, Schulz R. Inhibition of permeability transition pore opening by mitochondrial STAT3 and its role in myocardial ischemia/reperfusion. Basic Res Cardiol. 2010;105:771-85 pubmed publisher..However, CsA reduced infarct size to a similar extent in wildtype and STAT3-KO mice in vivo. Thus, STAT3 possibly contributes to cardioprotection by stimulation of respiration and inhibition of MPTP opening. ..
- Wei A, Liu T, Cortassa S, Winslow R, O ROURKE B. Mitochondrial Ca2+ influx and efflux rates in guinea pig cardiac mitochondria: low and high affinity effects of cyclosporine A. Biochim Biophys Acta. 2011;1813:1373-81 pubmed publisher..This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. ..
- Lin J, Hsiao K, Chen C, Wu C, Lin S, Chou Y, et al. High resolution melting analysis for the detection of SLC25A13 gene mutations in Taiwan. Clin Chim Acta. 2011;412:460-5 pubmed publisher..1638_1660dup/c.615+5G>A. HRM analysis is a simple, rapid and robust method for detecting SLC25A13 mutations in clinical laboratories. SLC25A13 mutations may not be a major contributor to the pathogenesis of HCC in Taiwan. ..
- Kallergi E, Andreadaki M, Kritsiligkou P, Katrakili N, Pozidis C, Tokatlidis K, et al. Targeting and maturation of Erv1/ALR in the mitochondrial intermembrane space. ACS Chem Biol. 2012;7:707-14 pubmed publisher..Both of these events must follow a specific sequential order to allow Erv1/ALR to reach the fully functional state, illustrating a new paradigm for protein maturation in the IMS...
- Pusnik M, Schmidt O, Perry A, Oeljeklaus S, Niemann M, Warscheid B, et al. Mitochondrial preprotein translocase of trypanosomatids has a bacterial origin. Curr Biol. 2011;21:1738-43 pubmed publisher..This suggests that the protein import channel in trypanosomes is a relic of an archaic protein transport system that was operational in the ancestor of all eukaryotes. ..
- Schmidt O, Harbauer A, Rao S, Eyrich B, Zahedi R, Stojanovski D, et al. Regulation of mitochondrial protein import by cytosolic kinases. Cell. 2011;144:227-39 pubmed publisher..We conclude that cytosolic kinases exert stimulatory and inhibitory effects on biogenesis and function of the TOM complex and thus regulate protein import into mitochondria. ..
- Qian X, Gebert M, Höpker J, Yan M, Li J, Wiedemann N, et al. Structural basis for the function of Tim50 in the mitochondrial presequence translocase. J Mol Biol. 2011;411:513-9 pubmed publisher..A protruding ?-hairpin of Tim50 is crucial for interaction with Tim23, providing a molecular basis for the cooperation of Tim50 and Tim23 in preprotein translocation to the protein-conducting channel of the mitochondrial inner membrane. ..
- Tanaka A, Cleland M, Xu S, Narendra D, Suen D, Karbowski M, et al. Proteasome and p97 mediate mitophagy and degradation of mitofusins induced by Parkin. J Cell Biol. 2010;191:1367-80 pubmed publisher..Inhibition of Drp1-mediated mitochondrial fission, the proteasome, or p97 prevents Parkin-induced mitophagy. ..
- Sedlic F, Sepac A, Pravdic D, Camara A, Bienengraeber M, Brzezinska A, et al. Mitochondrial depolarization underlies delay in permeability transition by preconditioning with isoflurane: roles of ROS and Ca2+. Am J Physiol Cell Physiol. 2010;299:C506-15 pubmed publisher..Such decrease in DeltaPsi(m) primarily attenuates mitochondrial ROS production, with consequential decrease in mitochondrial Ca(2+) uptake...
- Froese D, Kochan G, Muniz J, Wu X, Gileadi C, Ugochukwu E, et al. Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. J Biol Chem. 2010;285:38204-13 pubmed publisher..Together, our data point to a gatekeeping role for MMAA by favoring complex formation with MUT apoenzyme for AdoCbl assembly and releasing the AdoCbl-loaded holoenzyme from the complex, in a GTP-dependent manner. ..
- Schmidt O, Pfanner N, Meisinger C. Mitochondrial protein import: from proteomics to functional mechanisms. Nat Rev Mol Cell Biol. 2010;11:655-67 pubmed publisher..Protein translocases do not function as independent units but are integrated into dynamic networks and are connected to machineries that function in bioenergetics, mitochondrial morphology and coupling to the endoplasmic reticulum. ..