Featured
-
-
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
-
Article |
ATP13A2 deficiency disrupts lysosomal polyamine export
The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.
- Sarah van Veen
- , Shaun Martin
- & Peter Vangheluwe
-
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
-
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
-
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
-
Letter |
Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells
The cellular degradative machinery can be asymmetrically inherited upon haematopoietic-stem-cell division, which predicts the future metabolic and translational activation of their daughter cells.
- Dirk Loeffler
- , Arne Wehling
- & Timm Schroeder
-
Letter |
DEAD-box ATPases are global regulators of phase-separated organelles
RNA-dependent DEAD-box ATPases (DDXs) regulate the dynamics of phase-separated organelles, with ATP-bound DDXs promoting phase separation, and ATP hydrolysis inducing compartment disassembly and RNA release.
- Maria Hondele
- , Ruchika Sachdev
- & Karsten Weis
-
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
-
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
-
Matters Arising |
Mitochondrial fission requires DRP1 but not dynamins
- Tiago Branco Fonseca
- , Ángela Sánchez-Guerrero
- & Nuno Raimundo
-
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
-
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
-
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
-
Letter |
TIC236 links the outer and inner membrane translocons of the chloroplast
TIC236 is an inner-membrane protein that binds to the outer-membrane channel TOC75 to create a long, stable bridge that enables the transport of proteins into chloroplasts.
- Yih-Lin Chen
- , Lih-Jen Chen
- & Hsou-min Li
-
Letter |
Structure of the membrane-assembled retromer coat determined by cryo-electron tomography
The retromer complex (the vacuolar protein sorting heterotrimer Vps26–Vps29–Vps35) has been resolved in association with membranes and the sorting nexin protein Vps5 using cryo-electron tomography.
- Oleksiy Kovtun
- , Natalya Leneva
- & Brett M. Collins
-
Article |
Kinase-controlled phase transition of membraneless organelles in mitosis
The dual-specificity kinase DYRK3 acts as a central ‘dissolvase’, mediating the phase transitions of several types of membraneless organelles during mitosis.
- Arpan Kumar Rai
- , Jia-Xuan Chen
- & Lucas Pelkmans
-
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
-
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
-
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
-
Letter |
A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage
Sperm-activated lysosomes enhance proteostasis in nematode oocytes just before fertilization; this could prevent transmission of damaged proteins to the next generation and may explain the immortality of the germ-cell lineage.
- K. Adam Bohnert
- & Cynthia Kenyon
-
Letter |
Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3
The structure of yeast Hrd1 in complex with Hrd3 shows that Hrd1 forms an aqueous cavity with a lateral seal within the endoplasmic reticulum membrane, shedding light on how misfolded proteins are transported out of the endoplasmic reticulum.
- Stefan Schoebel
- , Wei Mi
- & Maofu Liao
-
Letter |
Applying systems-level spectral imaging and analysis to reveal the organelle interactome
Using confocal and lattice light sheet microscopy, the authors perform systems-level analysis of the organelle interactome in live cells, allowing them to visualize the frequency and locality of up to five-way interactions between different organelles.
- Alex M. Valm
- , Sarah Cohen
- & Jennifer Lippincott-Schwartz
-
Letter |
The mitochondrial Na+/Ca2+ exchanger is essential for Ca2+ homeostasis and viability
Conditional deletion of the mitochondrial Na+/Ca2+ exchanger NCLX in adult mouse hearts causes sudden death due to mitochondrial calcium overload, whereas its overexpression limits cell death elicited by ischaemia reperfusion injury and heart failure.
- Timothy S. Luongo
- , Jonathan P. Lambert
- & John W. Elrod
-
Letter |
Cytosolic proteostasis through importing of misfolded proteins into mitochondria
Proteins prone to aggregation in yeast are imported into mitochondria under stress conditions, suggesting that mitochondrial import and proteolysis may help to disaggregate proteins in the cytoplasm.
- Linhao Ruan
- , Chuankai Zhou
- & Rong Li
-
Letter |
Reconstitution of the tubular endoplasmic reticulum network with purified components
In the presence of GTP, a tubular endoplasmic reticulum network can be reconstituted with only two purified membrane proteins.
- Robert E. Powers
- , Songyu Wang
- & Tom A. Rapoport
-
Letter |
Newly born peroxisomes are a hybrid of mitochondrial and ER-derived pre-peroxisomes
Peroxisomes—tiny intracellular organelles that contain metabolic enzymes—are generated in mammalian cells by the fusion of structures that arise from both mitochondria and the endoplasmic reticulum.
- Ayumu Sugiura
- , Sevan Mattie
- & Heidi M. McBride
-
Letter |
MFN1 structures reveal nucleotide-triggered dimerization critical for mitochondrial fusion
Crystal structures of engineered human MFN1 in different stages of GTP hydrolysis provide insights into the GTP-induced conformational changes that promote MFN1 dimerization to bring about mitochondrial fusion.
- Yu-Lu Cao
- , Shuxia Meng
- & Song Gao
-
Letter |
The SND proteins constitute an alternative targeting route to the endoplasmic reticulum
Experiments in yeast cells show that three proteins—Snd1, Snd2 and Snd3—provide an alternative pathway for targeting of cellular proteins to the endoplasmic reticulum.
- Naama Aviram
- , Tslil Ast
- & Maya Schuldiner
-
Letter |
Multiple dynamin family members collaborate to drive mitochondrial division
The classical dynamin Dyn2 is required for mitochondrial division.
- Jason E. Lee
- , Laura M. Westrate
- & Gia K. Voeltz
-
Article |
Correcting mitochondrial fusion by manipulating mitofusin conformations
Specific intramolecular interactions of mitofusin 2 amino acid sequences either constrain or permit mitochondrial fusion and the addition of short peptides matching these sequences stabilize the fusion-constrained or fusion-permissive form, thus inhibiting or promoting mitochondrial fusion.
- Antonietta Franco
- , Richard N. Kitsis
- & Gerald W. Dorn II
-
Letter |
Mechanism of super-assembly of respiratory complexes III and IV
SCAF1 is always required for the interaction between the respiratory chain complexes III and IV, and in animals carrying only the short isoform of SCAF1, the respirasome is absent in most tissues, with the exception of heart and skeletal muscle, where COX7A2 is present instead of SCAF1.
- Sara Cogliati
- , Enrique Calvo
- & José Antonio Enriquez
-
Article |
The architecture of the mammalian respirasome
Respirasomes are supercomplexes of mitochondrial electron transport chain complexes that are responsible for cellular respiration and energy production; a cryo-electron microscopy structural study of the respirasome is presented.
- Jinke Gu
- , Meng Wu
- & Maojun Yang
-
Article |
The architecture of respiratory supercomplexes
Respirasomes are supercomplexes of mitochondrial electron transport chain complexes that are responsible for cellular respiration and energy production; cryo-electron microscopy structures of mammalian (sheep) respirasomes are presented.
- James A. Letts
- , Karol Fiedorczuk
- & Leonid A. Sazanov
-
Letter |
Accessory subunits are integral for assembly and function of human mitochondrial complex I
Gene-editing technology and large-scale proteomics are used to provide insights into the modular assembly of the human mitochondrial respiratory chain complex I, as well as identifying new assembly factors.
- David A. Stroud
- , Elliot E. Surgenor
- & Michael T. Ryan
-
Letter |
Atomic structure of the entire mammalian mitochondrial complex I
The atomic structure of ovine mitochondrial complex I is solved at 3.9 Å resolution, revealing that supernumerary subunits stabilize the complex and providing insight into the molecular basis of its function and regulation.
- Karol Fiedorczuk
- , James A. Letts
- & Leonid A. Sazanov
-
Letter |
Mitochondrial unfolded protein response controls matrix pre-RNA processing and translation
Acute protein folding stress in the mitochondrial matrix activates both increased chaperone availability within the matrix and reduced matrix-localized protein synthesis through translational inhibition.
- Christian Münch
- & J. Wade Harper
-
Article |
Synchronized mitochondrial and cytosolic translation programs
The genes encoding the subunits of oxidative phosphorylation complexes are split between the nuclear and mitochondrial genomes, but their translation is synchronized by signalling from the cytosol to the mitochondria.
- Mary T. Couvillion
- , Iliana C. Soto
- & L. Stirling Churchman
-
Letter |
Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response
In the context of mitochondrial genome heteroplasmy that causes defective oxidative phosphorylation in C. elegans, the ATFS-1-mediated mitochondrial unfolded protein response maintains the deleterious mitochondrial DNA in an attempt to recover oxidative phosphorylation activity and avoid cellular dysfunction.
- Yi-Fan Lin
- , Anna M. Schulz
- & Cole M. Haynes
-
Letter |
Primary cilia are not calcium-responsive mechanosensors
Mechanosensation, if it originates in primary cilia, is not via calcium signalling.
- M. Delling
- , A. A. Indzhykulian
- & D. E. Clapham
-
Letter |
Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry
Evidence that among the eukaryotic ancestor genes, those derived from the proto-mitochondrion have the closest evolutionary distances to their bacterial relatives.
- Alexandros A. Pittis
- & Toni Gabaldón
-
Article |
The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy
The PINK1 ubiquitin kinase is shown to recruit the two autophagy receptors NDP52 and OPTN to mitochondria to activate mitophagy directly, independently of the ubiquitin ligase parkin; once recruited to mitochondria, NDP52 and OPTN recruit autophagy initiation components, and parkin may amplify the phospho-ubiquitin signal generated by PINK1, resulting in robust autophagy induction.
- Michael Lazarou
- , Danielle A. Sliter
- & Richard J. Youle
-
Letter |
Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol
Mitochondrial dysfunction and cellular protein homeostasis failure are hallmarks of many diseases and age-associated pathologies; this study shows that the mitochondrial import defect of nuclear-encoded proteins triggers a cellular pathway, termed unfolded protein response activated by mistargeting of proteins (UPRam), that acts to minimize the stress caused by non-imported mitochondrial precursor proteins in order to sustain cellular protein homeostasis and organismal fitness.
- Lidia Wrobel
- , Ulrike Topf
- & Agnieszka Chacinska
-
Letter |
Mitochondrial reticulum for cellular energy distribution in muscle
Mitochondria are shown to form a conductive pathway throughout the cell in the form of a proton motive force, and throughout this network, mitochondrial protein localization seems to be varied, allowing optimized generation and utilization of the mitochondrial membrane potential; the rapid energy distribution network, which depends on conduction rather than diffusion, could explain how the muscle can rapidly respond to energy demands.
- Brian Glancy
- , Lisa M. Hartnell
- & Robert S. Balaban
-
Letter |
Regulation of mitochondrial morphology and function by stearoylation of TFR1
Mitochondria have essential functions within cells, and their dysfunction is linked to various disorders; here, the fatty acid stearic acid (C18:0), which is a dietary component, and the transferrin receptor (TFR1) are shown to regulate mitochondrial function.
- Deniz Senyilmaz
- , Sam Virtue
- & Aurelio A. Teleman
-
Letter |
A cytosolic network suppressing mitochondria-mediated proteostatic stress and cell death
A new pathway of mitochondria-mediated cell death termed mitochondrial precursor over-accumulation stress (mPOS) is identified that could explain the link between mitochondrial dysfunction and misfolding of cytosolic proteins during ageing and disease; the pathway is triggered not only by mutations affecting the core protein import machineries, but also by conditions that interfere with mitochondrial inner membrane integrity and function, and a large network of genes that suppress mPOS in favour of cell survival is also identified.
- Xiaowen Wang
- & Xin Jie Chen
-
Letter |
Eye-like ocelloids are built from different endosymbiotically acquired components
Dinoflagellate eye-like ocelloids are built from pre-existing organelles of disparate origin, including a cornea-like layer made of mitochondria and a retinal body made of anastomosing plastids.
- Gregory S. Gavelis
- , Shiho Hayakawa
- & Brian S. Leander
-
Letter |
Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus
In yeast, the novel protein Atg40 is enriched in the cortical and cytoplasmic endoplasmic reticulum (ER), and loads these ER subdomains into autophagosomes to facilitate ER autophagy; Atg39 localizes to the perinuclear ER and induces autophagic sequestration of part of the nucleus, thus ensuring cell survival under nitrogen-deprived conditions.
- Keisuke Mochida
- , Yu Oikawa
- & Hitoshi Nakatogawa
-
Letter |
Regulation of endoplasmic reticulum turnover by selective autophagy
The protein FAM134B is an endoplasmic reticulum (ER)-resident receptor that facilitates ER autophagy, and downregulation of this protein (mutations of which are also known to cause sensory neuropathy in humans) results in expanded ER structures and degeneration of mouse sensory neurons.
- Aliaksandr Khaminets
- , Theresa Heinrich
- & Ivan Dikic
-
Letter |
Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans
Mitophagy, a selective type of autophagy targeting mitochondria for degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content and longevity in Caenorhabditis elegans.
- Konstantinos Palikaras
- , Eirini Lionaki
- & Nektarios Tavernarakis