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Metabolic rewiring promotes anti-inflammatory effects of glucocorticoids
Glucocorticoids reprogram the mitochondrial metabolism of macrophages, resulting in increased and sustained production of the anti-inflammatory metabolite itaconate and, as a consequence, inhibition of the inflammatory response.
- Jean-Philippe Auger
- , Max Zimmermann
- & Gerhard Krönke
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Article
| Open AccessStress response silencing by an E3 ligase mutated in neurodegeneration
The E3 ligase SIFI is identified as a dedicated silencing factor of the integrated stress response, a finding that has implications for the development of therapeutics for neurodegenerative diseases caused by mitochondrial protein import stress.
- Diane L. Haakonsen
- , Michael Heider
- & Michael Rapé
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Article
| Open AccessMotion of VAPB molecules reveals ER–mitochondria contact site subdomains
High-speed molecular tracking is integrated with three-dimensional electron microscopy to map the diffusion distribution and ultrastructure of endoplasmic reticulum-mitochondria contact sites, revealing the ability of high-speed single-molecule imaging to map contact site interface structures and corresponding diffusion landscapes.
- Christopher J. Obara
- , Jonathon Nixon-Abell
- & Jennifer Lippincott-Schwartz
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Article
| Open AccessMitochondrial dysfunction abrogates dietary lipid processing in enterocytes
Mitochondria have a pivotal role in the transport of dietary lipids in enterocytes, a finding that might have relevance to understanding the aberrant gastrointestinal function in patients with mitochondrial disorders.
- Chrysanthi Moschandrea
- , Vangelis Kondylis
- & Manolis Pasparakis
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Perspective |
The power and potential of mitochondria transfer
The mechanisms by which mitochondria are transferred between cells and how intercellular mitochondria transfer regulates physiological processes and disease pathogenesis are discussed.
- Nicholas Borcherding
- & Jonathan R. Brestoff
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Article |
OPA1 helical structures give perspective to mitochondrial dysfunction
Cryo-electron microscopy structures of OPA1, mutations of which are associated with the disease dominant optic atrophy, provide insight into how structural features of OPA1 enable this protein to mediate mitochondrial-membrane fusion and remodelling.
- Sarah B. Nyenhuis
- , Xufeng Wu
- & Jenny E. Hinshaw
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Article |
Structural mechanism of mitochondrial membrane remodelling by human OPA1
Human OPA1 embeds itself into cardiolipin-containing membranes through a lipid-binding paddle domain, and OPA1 oligomerization through multiple assembly interfaces promotes the helical assembly of a flexible OPA1 lattice on the membrane, driving mitochondrial fusion in cells.
- Alexander von der Malsburg
- , Gracie M. Sapp
- & Halil Aydin
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Article |
Structural basis of mitochondrial protein import by the TIM23 complex
The cryo-electron microscopy structure of the mitochondrial TIM23 complex from Saccharomyces cerevisiae shows that Tim17 forms a protein translocation path.
- Sue Im Sim
- , Yuanyuan Chen
- & Eunyong Park
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Article
| Open AccessA cytosolic surveillance mechanism activates the mitochondrial UPR
We identify a highly controlled cytosolic surveillance mechanism that integrates independent mitochondrial stress signals to initiate the mitochondrial unfolded protein response (UPR), revealing a link between mitochondrial and cytosolic proteostasis.
- F. X. Reymond Sutandy
- , Ines Gößner
- & Christian Münch
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Article |
γ-Linolenic acid in maternal milk drives cardiac metabolic maturation
The switch from glucose- to fatty acid-dependent metabolism in cardiomyocytes of newborn mice is governed by γ-linolenic acid in maternal milk, which binds to retinoid X receptors, thereby causing a transcription-dependent metabolic transition.
- Ana Paredes
- , Raquel Justo-Méndez
- & Mercedes Ricote
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Article |
In situ architecture of the ER–mitochondria encounter structure
Integrative structural biology combining quantitative live imaging, cryo-correlative microscopy, subtomogram averaging and molecular modelling enables in situ determination of the structure of the endoplasmic reticulum–mitochondria encounter complex in yeast.
- Michael R. Wozny
- , Andrea Di Luca
- & Wanda Kukulski
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Article
| Open AccessSpatial mapping of mitochondrial networks and bioenergetics in lung cancer
A study describing an approach that combines imaging and profiling techniques to structurally and functionally analyse lung cancer in vivo, revealing heterogeneous mitochondrial networks and an association between bioenergetic phenotypes and mitochondrial organization and function.
- Mingqi Han
- , Eric A. Bushong
- & David B. Shackelford
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Article |
Macrophage fumarate hydratase restrains mtRNA-mediated interferon production
Inhibition of the tricarboxylic acid cycle enzyme fumarate hydratase leads to deregulation of cytokine production in macrophages, which has implications in human diseases such as systemic lupus erythematosus.
- Alexander Hooftman
- , Christian G. Peace
- & Luke A. J. O’Neill
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Article
| Open AccessFumarate induces vesicular release of mtDNA to drive innate immunity
Fumarate metabolism regulates the innate immune response through a mechanism in which high levels of fumarate result in the generation of mitochondrial-derived vesicles and the release of mitochondrial DNA into the cytosol, which activates inflammatory pathways.
- Vincent Zecchini
- , Vincent Paupe
- & Christian Frezza
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Article
| Open AccessMitochondrial complexome reveals quality-control pathways of protein import
An analysis of MitCOM—a comprehensive resource for the identification, organization and interaction of mitochondrial machineries and pathways in yeast—identifies a constitutive pathway for the removal of preproteins.
- Uwe Schulte
- , Fabian den Brave
- & Thomas Becker
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Article
| Open AccessNuclear-embedded mitochondrial DNA sequences in 66,083 human genomes
A study examining DNA transfer from mitochondria to the nucleus using whole-genome sequences from 66,083 people shows that this is an ongoing dynamic process in normal cells with distinct roles in different types of cancer.
- Wei Wei
- , Katherine R. Schon
- & Patrick F. Chinnery
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Article |
An LKB1–mitochondria axis controls TH17 effector function
OPA1 regulates the formation of the distinct mitochondrial morphology observed in T helper 17 cells, which influences cytokine expression via LKB1.
- Francesc Baixauli
- , Klara Piletic
- & Erika L. Pearce
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Article
| Open AccessOocytes maintain ROS-free mitochondrial metabolism by suppressing complex I
Oocytes prevent the production of reactive oxygen species by remodelling the mitochondrial electron transport chain through elimination of complex I, a strategy that enables their long-term viability.
- Aida Rodríguez-Nuevo
- , Ariadna Torres-Sanchez
- & Elvan Böke
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Article |
Defining mitochondrial protein functions through deep multiomic profiling
A multiomics resource characterizing human mitochondrial proteins enables identification of biological functions and supports genetic diagnosis of mitochondrial pathologies.
- Jarred W. Rensvold
- , Evgenia Shishkova
- & David J. Pagliarini
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Article |
Mitochondrial uncouplers induce proton leak by activating AAC and UCP1
Common protonophores—previously known as protein-independent proton translocators—activate mitochondrial heat production due to H+ leak through the ADP/ATP carrier and uncoupling protein 1.
- Ambre M. Bertholet
- , Andrew M. Natale
- & Yuriy Kirichok
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Article |
SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells
SLC25A39 and its paralogue SLC25A40 have redundant roles in the import of glutathione into mitochondria of mammalian cells.
- Ying Wang
- , Frederick S. Yen
- & Kıvanç Birsoy
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Article |
Structure and assembly of the mammalian mitochondrial supercomplex CIII2CIV
SCAF1 is solely required for supercomplex CIII2CIV assembly and is not involved in the formation of the respirasome (supercomplex CICIII2CIV)
- Irene Vercellino
- & Leonid A. Sazanov
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Article |
Distinct fission signatures predict mitochondrial degradation or biogenesis
Mitochondrial fission at the organelle periphery generates small daughter mitochondria that are removed by mitophagy whereas fission at the midzone leads to proliferation.
- Tatjana Kleele
- , Timo Rey
- & Suliana Manley
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Article |
Actin cables and comet tails organize mitochondrial networks in mitosis
During mitosis, complementary actin-based mechanisms ensure equal and random distributions of mitochondria among daughter cells following symmetrical cell division.
- Andrew S. Moore
- , Stephen M. Coscia
- & Erika L. F. Holzbaur
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Article
| Open AccessSulfur sequestration promotes multicellularity during nutrient limitation
Depriving unicellular Dictyostelium discoideum of nutrients generates reactive oxygen species that sequester cysteine within glutathione, which maintains this amoeba in a nonproliferating state that promotes aggregation into a multicellular organism.
- Beth Kelly
- , Gustavo E. Carrizo
- & Erika L. Pearce
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Article |
Nuclear sensing of breaks in mitochondrial DNA enhances immune surveillance
Breaks in mitochondrial DNA cause leakage of mitochondrial RNA into the cytoplasm, enhancing immune surveillance and synergizing with nuclear DNA damage to mount a robust type-I interferon immune response.
- Marco Tigano
- , Danielle C. Vargas
- & Agnel Sfeir
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Review Article |
Function and regulation of the divisome for mitochondrial fission
The functional and regulatory aspects of the ‘mitochondrial divisome’ are separated into core and accessory machinery, thus providing a mechanistic understanding of the process of mitochondrial fission.
- Felix Kraus
- , Krishnendu Roy
- & Michael T. Ryan
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Article |
Mitochondrial sorting and assembly machinery operates by β-barrel switching
Proteins are inserted into the outer mitochondrial membrane by the mitochondrial sorting and assembly machinery, two structural forms of which are presented here, suggesting the mechanism involved.
- Hironori Takeda
- , Akihisa Tsutsumi
- & Toshiya Endo
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Article |
Small-molecule inhibitors of human mitochondrial DNA transcription
Inhibitors of mitochondrial transcription that target human mitochondrial RNA polymerase provide a chemical biology tool for studying the role of mitochondrial DNA expression in a wide range of pathologies.
- Nina A. Bonekamp
- , Bradley Peter
- & Nils-Göran Larsson
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Article |
SLC25A51 is a mammalian mitochondrial NAD+ transporter
SLC25A51 is identified as a transporter of intact NAD+ into mammalian mitochondria and is required to maintain the mitochondrial NAD+ pool and respiratory function.
- Timothy S. Luongo
- , Jared M. Eller
- & Joseph A. Baur
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Article |
Na+ controls hypoxic signalling by the mitochondrial respiratory chain
Na+ controls the function of the mitochondrial oxidative phosphorylation system and hypoxic redox signalling through an unexpected interaction with phospholipids.
- Pablo Hernansanz-Agustín
- , Carmen Choya-Foces
- & Antonio Martínez-Ruiz
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Matters Arising |
In vivo quantification of mitochondrial membrane potential
- Nathaniel M. Alpert
- , Matthieu Pelletier-Galarneau
- & Georges El Fakhri
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Article |
A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing
An interbacterial toxin that catalyses the deamination of cytidines within double-stranded DNA forms part of a CRISPR-free, RNA-free base editing system that enables manipulation of human mitochondrial DNA.
- Beverly Y. Mok
- , Marcos H. de Moraes
- & David R. Liu
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Article |
Mitochondrial stress is relayed to the cytosol by an OMA1–DELE1–HRI pathway
A genome-wide CRISPR interference screen shows that a signalling pathway involving OMA1, DELE1 and the eIF2α kinase HRI relays mitochondrial stress to the cytosol to trigger the integrated stress response.
- Xiaoyan Guo
- , Giovanni Aviles
- & Martin Kampmann
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Article |
Glucagon stimulates gluconeogenesis by INSP3R1-mediated hepatic lipolysis
A role and mechanism of action are identified for INSP3R1 in the stimulation of hepatic gluconeogenesis and mitochondrial oxidation by glucagon, suggesting that INSP3R1 may be a target for ameliorating dysregulation of hepatic glucose metabolism.
- Rachel J. Perry
- , Dongyan Zhang
- & Gerald I. Shulman
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Article |
Lipid signalling drives proteolytic rewiring of mitochondria by YME1L
Under conditions such as hypoxia or starvation, an mTORC1-lipid signalling pathway initiates mitochondrial proteolysis by YME1L.
- Thomas MacVicar
- , Yohsuke Ohba
- & Thomas Langer
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Article |
The ADP/ATP translocase drives mitophagy independent of nucleotide exchange
A CRISPR–Cas9 genetic screen shows that the adenine nucleotide translocator is required for mitophagy and that this role is independent of its nucleotide translocase activity.
- Atsushi Hoshino
- , Wei-jia Wang
- & Zoltan Arany
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Article |
Structure of the mitochondrial import gate reveals distinct preprotein paths
The high-resolution cryo-electron microscopy structure of the yeast translocase of the outer mitochondrial membrane reveals key features of mitochondrial protein import that are conserved in all eukaryotes.
- Yuhei Araiso
- , Akihisa Tsutsumi
- & Toshiya Endo
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Article |
Identification of an ATP-sensitive potassium channel in mitochondria
The pore-forming and ATP-binding subunits of a mitochondrial protein complex that mediates ATP-dependent potassium currents are identified and characterized, revealing the role of this channel in mitochondrial physiology and pathologies.
- Angela Paggio
- , Vanessa Checchetto
- & Diego De Stefani
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Letter |
Structure and assembly of the mitochondrial membrane remodelling GTPase Mgm1
Crystal and electron cryo-tomography structures of Mgm1 from Chaetomium thermophilum reveal that Mgm1 forms bent tetramers, which further assemble into helical filaments on both positively and negatively curved membranes.
- Katja Faelber
- , Lea Dietrich
- & Oliver Daumke
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Matters Arising |
Mitochondrial fission requires DRP1 but not dynamins
- Tiago Branco Fonseca
- , Ángela Sánchez-Guerrero
- & Nuno Raimundo
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Article |
Mitochondrial protein translocation-associated degradation
In Saccharomyces cerevisiae, Ubx2 promotes clearing trapped precursor proteins from the channel of the translocase of the outer membrane, in a translocation-associated degradation pathway that maintains the protein import capacity of mitochondria.
- Christoph U. Mårtensson
- , Chantal Priesnitz
- & Thomas Becker
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Letter |
Mitochondrial fragmentation drives selective removal of deleterious mtDNA in the germline
An in situ hybridization approach is used to visualize mitochondrial DNA germline selection in Drosophila, revealing the role of mitochondrial fragmentation in the selection against deleterious mutations.
- Toby Lieber
- , Swathi P. Jeedigunta
- & Thomas R. Hurd
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Letter |
A potassium channel β-subunit couples mitochondrial electron transport to sleep
Sleep deprivation in Drosophila elevates reactive oxygen species in sleep-promoting neurons, leading to changes in potassium currents and spiking activity and thereby connecting energy metabolism, oxidative stress, and sleep.
- Anissa Kempf
- , Seoho M. Song
- & Gero Miesenböck
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Letter |
Mitochondrial complex III is essential for suppressive function of regulatory T cells
Specific ablation of mitochondrial complex III subunits in Treg cells in mice results in inflammatory disease, altered Treg gene expression and defective Treg function, indicating a key functional role for mitochondrial complex III in Treg cells.
- Samuel E. Weinberg
- , Benjamin D. Singer
- & Navdeep S. Chandel
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Article |
De novo NAD+ synthesis enhances mitochondrial function and improves health
Genetic or pharmacological inhibition of α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase increases NAD+ and improves mitochondrial function in nematodes and mice, and may have therapeutic potential in kidney and liver disease.
- Elena Katsyuba
- , Adrienne Mottis
- & Johan Auwerx
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Article |
Structural basis of mitochondrial receptor binding and constriction by DRP1
Cryo-electron microscopy is used to resolve the structure of human dynamin-related protein 1 co-assembled with its receptor mitochondrial dynamics protein of 49 kDa, along with an analysis of structure- and disease-based mutations.
- Raghav Kalia
- , Ray Yu-Ruei Wang
- & Adam Frost
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Letter |
Mitochondrial translation requires folate-dependent tRNA methylation
Mammalian mitochondria use folate-bound one-carbon units generated by the enzyme SHMT2 to methylate tRNA, and this modification is required for mitochondrial translation and thus oxidative phosphorylation.
- Raphael J. Morscher
- , Gregory S. Ducker
- & Joshua D. Rabinowitz
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Letter |
Mitochondria–lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis
Formation of inter-organelle contacts between mitochondria and lysosomes, regulated by lysosomal RAB7 GTP hydrolysis, allows for bidirectional regulation of mitochondrial and lysosomal dynamics.
- Yvette C. Wong
- , Daniel Ysselstein
- & Dimitri Krainc