Optogenetic control of mitochondrial protonmotive force to impact cellular stress resistance.


:Mitochondrial respiration generates an electrochemical proton gradient across the mitochondrial inner membrane called protonmotive force (PMF) to drive diverse functions and synthesize ATP. Current techniques to manipulate the PMF are limited to its dissipation; yet, there is no precise and reversible method to increase the PMF. To address this issue, we aimed to use an optogenetic approach and engineered a mitochondria-targeted light-activated proton pump that we name mitochondria-ON (mtON) to selectively increase the PMF in Caenorhabditis elegans. Here we show that mtON photoactivation increases the PMF in a dose-dependent manner, supports ATP synthesis, increases resistance to mitochondrial toxins, and modulates energy-sensing behavior. Moreover, transient mtON activation during hypoxic preconditioning prevents the well-characterized adaptive response of hypoxia resistance. Our results show that optogenetic manipulation of the PMF is a powerful tool to modulate metabolism and cell signaling.




EMBO reports


Berry BJ,Trewin AJ,Milliken AS,Baldzizhar A,Amitrano AM,Lim Y,Kim M,Wojtovich AP




Has Abstract


2020-04-03 00:00:00












  • Endogenous electric currents might guide rostral migration of neuroblasts.

    abstract::Mechanisms that guide directional migration of neuroblasts from the subventricular zone (SVZ) are not well understood. We report here that endogenous electric currents serve as a guidance cue for neuroblast migration. We identify the existence of naturally occurring electric currents (1.5±0.6 μA/cm(2), average field s...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Cao L,Wei D,Reid B,Zhao S,Pu J,Pan T,Yamoah E,Zhao M

    更新日期:2013-02-01 00:00:00

  • The human GINS complex binds to and specifically stimulates human DNA polymerase alpha-primase.

    abstract::The eukaryotic GINS complex has an essential role in the initiation and elongation phases of genome duplication. It is composed of four paralogous subunits--Sld5, Psf1, Psf2 and Psf3--which are ubiquitous and evolutionarily conserved in eukaryotic organisms. Here, we report the biochemical characterization of the huma...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: De Falco M,Ferrari E,De Felice M,Rossi M,Hübscher U,Pisani FM

    更新日期:2007-01-01 00:00:00

  • Acetyltransferase GCN5 regulates autophagy and lysosome biogenesis by targeting TFEB.

    abstract::Accumulating evidence highlights the role of histone acetyltransferase GCN5 in the regulation of cell metabolism in metazoans. Here, we report that GCN5 is a negative regulator of autophagy, a lysosome-dependent catabolic mechanism. In animal cells and Drosophila, GCN5 inhibits the biogenesis of autophagosomes and lys...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Wang Y,Huang Y,Liu J,Zhang J,Xu M,You Z,Peng C,Gong Z,Liu W

    更新日期:2020-01-07 00:00:00

  • Snail genes at the crossroads of symmetric and asymmetric processes in the developing mesoderm.

    abstract::Retinoic acid (RA) signalling ensures that vertebrate mesoderm segmentation is bilaterally synchronized, and corrects transient interferences from asymmetric left-right (L-R) signals involved in organ lateralization. Snail genes participate in both these processes and, although they are expressed symmetrically in the ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Morales AV,Acloque H,Ocaña OH,de Frutos CA,Gold V,Nieto MA

    更新日期:2007-01-01 00:00:00

  • The solution structure of PapGII from uropathogenic Escherichia coli and its recognition of glycolipid receptors.

    abstract::Uropathogenic Escherichia coli (UPEC) is the primary cause of symptomatic urinary tract infection. The P-pili, a bacterial surface organelle, mediates the bacterial host--cell adhesion. The PapG adhesin has generated much interest in recent years, not only because of its clinical value, i.e. in the prevention of micro...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Sung MA,Fleming K,Chen HA,Matthews S

    更新日期:2001-07-01 00:00:00

  • Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing.

    abstract::Extracellular vesicles (EVs) have been shown to carry microbial components and function in the host defense against infections. In this study, we demonstrate that Mycobacterium tuberculosis (M.tb) RNA is delivered into macrophage-derived EVs through an M.tb SecA2-dependent pathway and that EVs released from M.tb-infec...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Cheng Y,Schorey JS

    更新日期:2019-03-01 00:00:00

  • The interface between the ubiquitin family and the DNA damage response.

    abstract::The crucial role of ubiquitin signalling in genome-integrity maintenance was first recognized in 1987 by Stefan Jentsch and Alex Varshavsky, who showed that Rad6-the repair protein involved in DNA damage tolerance-is a ubiquitin-conjugating enzyme. Although this discovery inspired extensive research and led to the dis...

    journal_title:EMBO reports



    authors: Lukas J

    更新日期:2010-12-01 00:00:00

  • The O-linked N-acetylglucosamine modification in cellular signalling and the immune system. 'Protein modifications: beyond the usual suspects' review series.

    abstract::The intracellular modification of proteins by the addition of a single O-linked N-acetylglucosamine (O-GlcNAc) molecule is a ubiquitous post-translational modification in eukaryotic cells. It is catalysed by O-linked N-acetylglucosaminyltransferase, which attaches O-GlcNAc to serine/threonine residues, and it is count...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Golks A,Guerini D

    更新日期:2008-08-01 00:00:00

  • The protein phosphatase 1 regulator PNUTS is a new component of the DNA damage response.

    abstract::The function of protein phosphatase 1 nuclear-targeting subunit (PNUTS)--one of the most abundant nuclear-targeting subunits of protein phosphatase 1 (PP1c)--remains largely uncharacterized. We show that PNUTS depletion by small interfering RNA activates a G2 checkpoint in unperturbed cells and prolongs G2 checkpoint ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Landsverk HB,Mora-Bermúdez F,Landsverk OJ,Hasvold G,Naderi S,Bakke O,Ellenberg J,Collas P,Syljuåsen RG,Küntziger T

    更新日期:2010-11-01 00:00:00

  • Alternative editing of cytochrome c oxidase III mRNA in trypanosome mitochondria generates protein diversity.

    abstract::Trypanosomes use RNA editing to produce most functional mitochondrial messenger RNA. Precise insertion and deletion of hundreds of uridines is necessary to make full-length cytochrome c oxidase III (COXIII) mRNA. We show that COXIII mRNA can be alternatively edited by a mechanism using an alternative guide RNA to make...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Ochsenreiter T,Hajduk SL

    更新日期:2006-11-01 00:00:00

  • The evolution of human endurance: Research on the biology of extreme endurance gives insights into its evolution in humans and animals.

    abstract::Research into the extreme feats of endurance that humans and some animals achieve has uncovered a range of metabolic and physiological adaptations along with their evolutionary origins. ...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Hunter P

    更新日期:2019-11-05 00:00:00

  • Reverse genetics in the mosquito Anopheles gambiae: targeted disruption of the Defensin gene.

    abstract::Anopheles gambiae, the major vector of human malaria parasite, is an important insect model to study vector-parasite interactions. Here, we developed a simple in vivo double-stranded RNA (dsRNA) knockout approach to determine the function of the mosquito antimicrobial peptide gene Defensin. We injected dsRNA into adul...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Blandin S,Moita LF,Köcher T,Wilm M,Kafatos FC,Levashina EA

    更新日期:2002-09-01 00:00:00

  • Redox activation of ATM enhances GSNOR translation to sustain mitophagy and tolerance to oxidative stress.

    abstract::The denitrosylase S-nitrosoglutathione reductase (GSNOR) has been suggested to sustain mitochondrial removal by autophagy (mitophagy), functionally linking S-nitrosylation to cell senescence and aging. In this study, we provide evidence that GSNOR is induced at the translational level in response to hydrogen peroxide ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Cirotti C,Rizza S,Giglio P,Poerio N,Allega MF,Claps G,Pecorari C,Lee JH,Benassi B,Barilà D,Robert C,Stamler JS,Cecconi F,Fraziano M,Paull TT,Filomeni G

    更新日期:2020-11-27 00:00:00

  • PINK1 phosphorylates Drp1S616 to regulate mitophagy-independent mitochondrial dynamics.

    abstract::Impairment of PINK1/parkin-mediated mitophagy is currently proposed to be the molecular basis of mitochondrial abnormality in Parkinson's disease (PD). We here demonstrate that PINK1 directly phosphorylates Drp1 on S616. Drp1S616 phosphorylation is significantly reduced in cells and mouse tissues deficient for PINK1, ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Han H,Tan J,Wang R,Wan H,He Y,Yan X,Guo J,Gao Q,Li J,Shang S,Chen F,Tian R,Liu W,Liao L,Tang B,Zhang Z

    更新日期:2020-08-05 00:00:00

  • A genetic system for biasing the sex ratio in mice.

    abstract::Biasing the sex ratio of populations of different organisms, including plants, insects, crustacean, and fish, has been demonstrated by genetic and non-genetic approaches. However, biasing the sex ratio of mammalian populations has not been demonstrated genetically. Here, we provide a first proof of concept for such a ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Yosef I,Edry-Botzer L,Globus R,Shlomovitz I,Munitz A,Gerlic M,Qimron U

    更新日期:2019-08-01 00:00:00

  • Bringing order to translation: the contributions of transfer RNA anticodon-domain modifications.

    abstract::The biosynthesis of RNA includes its post-transcriptional modifications, and the crucial functions of these modifications have supported their conservation within all three kingdoms. For example, the modifications located within or adjacent to the anticodon of the transfer RNA (tRNA) enhance the accuracy of codon bind...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Agris PF

    更新日期:2008-07-01 00:00:00

  • A matter of choice: the establishment of sister chromatid cohesion.

    abstract::Sister chromatid cohesion is the basis for the recognition of chromosomal DNA replication products for their bipolar segregation in mitosis. Fundamental to sister chromatid cohesion is the ring-shaped cohesin complex, which is loaded onto chromosomes long before the initiation of DNA replication and is thought to hold...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Uhlmann F

    更新日期:2009-10-01 00:00:00

  • The 18S ribosomal RNA m6 A methyltransferase Mettl5 is required for normal walking behavior in Drosophila.

    abstract::RNA modifications have recently emerged as an important layer of gene regulation. N6-methyladenosine (m6 A) is the most prominent modification on eukaryotic messenger RNA and has also been found on noncoding RNA, including ribosomal and small nuclear RNA. Recently, several m6 A methyltransferases were identified, unco...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Leismann J,Spagnuolo M,Pradhan M,Wacheul L,Vu MA,Musheev M,Mier P,Andrade-Navarro MA,Graille M,Niehrs C,Lafontaine DL,Roignant JY

    更新日期:2020-07-03 00:00:00

  • PHF6 promotes non-homologous end joining and G2 checkpoint recovery.

    abstract::The cellular response to DNA breaks is influenced by chromatin compaction. To identify chromatin regulators involved in the DNA damage response, we screened for genes that affect recovery following DNA damage using an RNAi library of chromatin regulators. We identified genes involved in chromatin remodeling, sister ch...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Warmerdam DO,Alonso-de Vega I,Wiegant WW,van den Broek B,Rother MB,Wolthuis RM,Freire R,van Attikum H,Medema RH,Smits VA

    更新日期:2020-01-07 00:00:00

  • Structure of the ubiquitin-binding zinc finger domain of human DNA Y-polymerase eta.

    abstract::The ubiquitin-binding zinc finger (UBZ) domain of human DNA Y-family polymerase (pol) eta is important in the recruitment of the polymerase to the stalled replication machinery in translesion synthesis. Here, we report the solution structure of the pol eta UBZ domain and its interaction with ubiquitin. We show that th...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Bomar MG,Pai MT,Tzeng SR,Li SS,Zhou P

    更新日期:2007-03-01 00:00:00

  • The role of miRNAs and endogenous siRNAs in maternal-to-zygotic reprogramming and the establishment of pluripotency.

    abstract::RNA silencing is a complex of mechanisms that regulate gene expression through small RNA molecules. The microRNA (miRNA) pathway is the most common of these in mammals. Genome-encoded miRNAs suppress translation in a sequence-specific manner and facilitate shifts in gene expression during developmental transitions. He...

    journal_title:EMBO reports

    pub_type: 杂志文章,评审


    authors: Svoboda P,Flemr M

    更新日期:2010-08-01 00:00:00

  • An incoherent feed-forward loop mediates robustness and tunability in a plant immune network.

    abstract::Immune signaling networks must be tunable to alleviate fitness costs associated with immunity and, at the same time, robust against pathogen interferences. How these properties mechanistically emerge in plant immune signaling networks is poorly understood. Here, we discovered a molecular mechanism by which the model p...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Mine A,Nobori T,Salazar-Rondon MC,Winkelmüller TM,Anver S,Becker D,Tsuda K

    更新日期:2017-03-01 00:00:00

  • Involvement of state transitions in the switch between linear and cyclic electron flow in Chlamydomonas reinhardtii.

    abstract::The energetic metabolism of photosynthetic organisms is profoundly influenced by state transitions and cyclic electron flow around photosystem I. The former involve a reversible redistribution of the light-harvesting antenna between photosystem I and photosystem II and optimize light energy utilization in photosynthes...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Finazzi G,Rappaport F,Furia A,Fleischmann M,Rochaix JD,Zito F,Forti G

    更新日期:2002-03-01 00:00:00

  • AKT isoforms modulate Th1-like Treg generation and function in human autoimmune disease.

    abstract::Foxp3(+) regulatory T cells (Tregs) exhibit plasticity, which dictates their function. Secretion of the inflammatory cytokine IFNγ, together with the acquisition of a T helper 1 (Th1)-like effector phenotype as observed in cancer, infection, and autoimmune diseases, is associated with loss of Treg suppressor function ...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Kitz A,de Marcken M,Gautron AS,Mitrovic M,Hafler DA,Dominguez-Villar M

    更新日期:2016-08-01 00:00:00

  • RNase H eliminates R-loops that disrupt DNA replication but is nonessential for efficient DSB repair.

    abstract::In Saccharomyces cerevisiae, genome stability depends on RNases H1 and H2, which remove ribonucleotides from DNA and eliminate RNA-DNA hybrids (R-loops). In Schizosaccharomyces pombe, RNase H enzymes were reported to process RNA-DNA hybrids produced at a double-strand break (DSB) generated by I-PpoI meganuclease. Howe...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Zhao H,Zhu M,Limbo O,Russell P

    更新日期:2018-05-01 00:00:00

  • Two internal ribosome entry sites mediate the translation of p53 isoforms.

    abstract::The p53 tumour suppressor protein has a crucial role in cell-cycle arrest and apoptosis. Previous reports show that the p53 messenger RNA is translated to produce an amino-terminal-deleted isoform (DeltaN-p53) from an internal initiation codon, which acts as a dominant-negative inhibitor of full-length p53. Here, we s...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Ray PS,Grover R,Das S

    更新日期:2006-04-01 00:00:00

  • Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock.

    abstract::In mammals, immediate-early transcription of the Period 1 (Per1) gene is crucial for resetting the mammalian circadian clock. Here, we show that CLOCK is a real signalling molecule that mediates the serum-evoked rapid induction of Per1 in fibroblasts through the Ca2+-dependent protein kinase C (PKC) pathway. Stimulati...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Shim HS,Kim H,Lee J,Son GH,Cho S,Oh TH,Kang SH,Seen DS,Lee KH,Kim K

    更新日期:2007-04-01 00:00:00

  • Yarrowia lipolytica Pex20p, Saccharomyces cerevisiae Pex18p/Pex21p and mammalian Pex5pL fulfil a common function in the early steps of the peroxisomal PTS2 import pathway.

    abstract::Import of peroxisomal matrix proteins is essential for peroxisome biogenesis. Genetic and biochemical studies using a variety of different model systems have led to the discovery of 23 PEX genes required for this process. Although it is generally believed that, in contrast to mitochondria and chloroplasts, translocati...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Einwächter H,Sowinski S,Kunau WH,Schliebs W

    更新日期:2001-11-01 00:00:00

  • A non-canonical UBA-UBL interaction forms the linear-ubiquitin-chain assembly complex.

    abstract::HOIL-1L and its binding partner HOIP are essential components of the E3-ligase complex that generates linear ubiquitin (Ub) chains, which are critical regulators of NF-κB activation. Using crystallographic and mutational approaches, we characterize the unexpected structural basis for the specific interaction between t...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Yagi H,Ishimoto K,Hiromoto T,Fujita H,Mizushima T,Uekusa Y,Yagi-Utsumi M,Kurimoto E,Noda M,Uchiyama S,Tokunaga F,Iwai K,Kato K

    更新日期:2012-05-01 00:00:00

  • Resistance of glia-like central and peripheral neural stem cells to genetically induced mitochondrial dysfunction--differential effects on neurogenesis.

    abstract::Mitochondria play a central role in stem cell homeostasis. Reversible switching between aerobic and anaerobic metabolism is critical for stem cell quiescence, multipotency, and differentiation, as well as for cell reprogramming. However, the effect of mitochondrial dysfunction on neural stem cell (NSC) function is uns...

    journal_title:EMBO reports

    pub_type: 杂志文章


    authors: Díaz-Castro B,Pardal R,García-Flores P,Sobrino V,Durán R,Piruat JI,López-Barneo J

    更新日期:2015-11-01 00:00:00