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university of tampere: faculty of medicine and life sciences: research: howy jacobs - mitochondrial genetics - mitochondrial biology:
Lääketieteen ja biotieteiden tiedekunta FinMIT Centre of Exellence in research on  mitochondrial disease and ageing University of Tampere Institute of Biomedical Technology - IBT
Howy Jacobs - Mitochondrial Genetics - Mitochondrial Biology

Previous publications

Saari S, Andjelković A, Garcia GS, Jacobs HT, Oliveira MT
Expression of Ciona intestinalis AOX causes male reproductive defects in Drosophila melanogaster.
BMC Dev Biol ;17(1)9, 2017

Salminen TS, Oliveira MT, Cannino G, Lillsunde P, Jacobs HT, Kaguni LS
Mitochondrial genotype modulates mtDNA copy number and organismal phenotype in Drosophila.
Mitochondrion ;2017

Mills EL, Kelly B, Logan A, Costa ASH, Varma M, Bryant CE, Tourlomousis P, Däbritz JHM, Gottlieb E, Latorre I, Corr SC, McManus G, Ryan D, Jacobs HT, Szibor M, Xavier RJ, Braun T, Frezza C, Murphy MP, O'Neill LA
Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages.
Cell ;167(2)457-470.e13, 2016

Andjelković A, Kemppainen KK, Jacobs HT
Ligand-Bound GeneSwitch Causes Developmental Aberrations in Drosophila that Are Alleviated by the Alternative Oxidase.
G3 (Bethesda) ;6(9)2839-46, 2016

Shi Y, Posse V, Zhu X, Hyvärinen AK, Jacobs HT, Falkenberg M, Gustafsson CM
Mitochondrial transcription termination factor 1 directs polar replication fork pausing.
Nucleic Acids Res ;44(12)5732-42, 2016

El-Khoury R, Kaulio E, Lassila KA, Crowther DC, Jacobs HT, Rustin P
Expression of the alternative oxidase mitigates beta-amyloid production and toxicity in model systems.
Free Radic Biol Med ;2016

Kemppainen E, George J, Garipler G, Tuomela T, Kiviranta E, Soga T, Dunn CD, Jacobs HT
Correction: Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth.
PLoS One ;11(3)e0151421, 2016

Kemppainen E, George J, Garipler G, Tuomela T, Kiviranta E, Soga T, Dunn CD, Jacobs HT
Mitochondrial Dysfunction Plus High-Sugar Diet Provokes a Metabolic Crisis That Inhibits Growth.
PLoS One ;11(1)e0145836, 2016

Andjelković A, Oliveira MT, Cannino G, Yalgin C, Dhandapani PK, Dufour E, Rustin P, Szibor M, Jacobs HT
Diiron centre mutations in Ciona intestinalis alternative oxidase abolish enzymatic activity and prevent rescue of cytochrome oxidase deficiency in flies.
Sci Rep ;2015

Syrjänen L, Valanne S, Kuuslahti M, Tuomela T, Sriram A, Sanz A, Jacobs HT, Rämet M, Parkkila S
β carbonic anhydrase is required for female fertility in Drosophila melanogaster.
Front Zool ;2015

Holmes JB, Akman G, Wood SR, Sakhuja K, Cerritelli SM, Moss C, Bowmaker MR, Jacobs HT, Crouch RJ, Holt IJ
Primer retention owing to the absence of RNase H1 is catastrophic for mitochondrial DNA replication.
Proc Natl Acad Sci U S A ;112(30)9334-9, 2015

Lewis SC, Joers P, Willcox S, Griffith JD, Jacobs HT, Hyman BC
A rolling circle replication mechanism produces multimeric lariats of mitochondrial DNA in Caenorhabditis elegans.
PLoS Genet ;11(2)e1004985, 2015

Gospodaryov DV, Lushchak OV, Rovenko BM, Perkhulyn NV, Gerards M, Tuomela T, Jacobs HT
Ciona intestinalis NADH dehydrogenase NDX confers stress-resistance and extended lifespan on Drosophila.
Biochim Biophys Acta ;1837(11)1861-1869, 2014

Kemppainen KK, Kemppainen E, Jacobs HT
The alternative oxidase AOX does not rescue the phenotype of tko25t mutant flies.
G3 (Bethesda) ;4(10)2013-21, 2014

Holt IJ, Jacobs HT
Unique features of DNA replication in mitochondria: a functional and evolutionary perspective.
Bioessays ;36(11)1024-31, 2014

Fukuoh A, Cannino G, Gerards M, Buckley S, Kazancioglu S, Scialo F, Lihavainen E, Ribeiro A, Dufour E, Jacobs HT
Screen for mitochondrial DNA copy number maintenance genes reveals essential role for ATP synthase.
Mol Syst Biol ;2014

El-Khoury R, Kemppainen KK, Dufour E, Szibor M, Jacobs HT, Rustin P
Engineering the alternative oxidase gene to better understand and counteract mitochondrial defects: state of the art and perspectives.
Br J Pharmacol ;171(8)2243-9, 2014

Vartiainen S, Chen S, George J, Tuomela T, Luoto KR, O'Dell KM, Jacobs HT
Phenotypic rescue of a Drosophila model of mitochondrial ANT1 disease.
Dis Model Mech ;7(6)635-48, 2014

Kemppainen KK, Rinne J, Sriram A, Lakanmaa M, Zeb A, Tuomela T, Popplestone A, Singh S, Sanz A, Rustin P, Jacobs HT
Expression of alternative oxidase in Drosophila ameliorates diverse phenotypes due to cytochrome oxidase deficiency.
Hum Mol Genet ;23(8)2078-93, 2014

Cannino G, El-Khoury R, Pirinen M, Hutz B, Rustin P, Jacobs HT, Dufour E
Glucose modulates respiratory complex I activity in response to acute mitochondrial dysfunction.
J Biol Chem ;287(46)38729-40, 2012

Stefanatos R, Sriram A, Kiviranta E, Mohan A, Ayala V, Jacobs HT, Pamplona R, Sanz A
dj-1β regulates oxidative stress, insulin-like signaling and development in Drosophila melanogaster.
Cell Cycle ;11(20)3876-86, 2012

Chen S, Oliveira MT, Sanz A, Kemppainen E, Fukuoh A, Schlicht B, Kaguni LS, Jacobs HT
A cytoplasmic suppressor of a nuclear mutation affecting mitochondrial functions in Drosophila.
Genetics ;192(2)483-93, 2012

Schiff M, Bénit P, Jacobs HT, Vockley J, Rustin P
Therapies in inborn errors of oxidative metabolism.
Trends Endocrinol Metab ;23(9)488-95, 2012

Humphrey DM, Parsons RB, Ludlow ZN, Riemensperger T, Esposito G, Verstreken P, Jacobs HT, Birman S, Hirth F
Alternative oxidase rescues mitochondria-mediated dopaminergic cell loss in Drosophila.
Hum Mol Genet ;21(12)2698-712, 2012

Rubio-Cosials A, Sidow JF, Jiménez-Menéndez N, Fernández-Millán P, Montoya J, Jacobs HT, Coll M, Bernadó P, Solà M
Human mitochondrial transcription factor A induces a U-turn structure in the light strand promoter.
Nat Struct Mol Biol ;18(11)1281-9, 2011

Häkkinen A, Healy S, Jacobs HT, Ribeiro AS
Genome wide study of NF-Y type CCAAT boxes in unidirectional and bidirectional promoters in human and mouse.
J Theor Biol ;281(1)74-83, 2011

Hyvärinen AK, Pohjoismäki JL, Holt IJ, Jacobs HT
Overexpression of MTERFD1 or MTERFD3 impairs the completion of mitochondrial DNA replication.
Mol Biol Rep ;38(2)1321-8, 2011

Hyvärinen AK, Kumanto MK, Marjavaara SK, Jacobs HT
Effects on mitochondrial transcription of manipulating mTERF protein levels in cultured human HEK293 cells.
BMC Mol Biol ;2010

Jiménez-Menéndez N, Fernández-Millán P, Rubio-Cosials A, Arnan C, Montoya J, Jacobs HT, Bernadó P, Coll M, Usón I, Solà M
Human mitochondrial mTERF wraps around DNA through a left-handed superhelical tandem repeat.
Nat Struct Mol Biol ;17(7)891-3, 2010

Chua YL, Dufour E, Dassa EP, Rustin P, Jacobs HT, Taylor CT, Hagen T
Stabilization of hypoxia-inducible factor-1alpha protein in hypoxia occurs independently of mitochondrial reactive oxygen species production.
J Biol Chem ;285(41)31277-84, 2010

Pohjoismäki JL, Goffart S, Taylor RW, Turnbull DM, Suomalainen A, Jacobs HT, Karhunen PJ
Developmental and pathological changes in the human cardiac muscle mitochondrial DNA organization, replication and copy number.
PLoS One ;5(5)e10426, 2010

Sanz A, Soikkeli M, Portero-Otín M, Wilson A, Kemppainen E, McIlroy G, Ellilä S, Kemppainen KK, Tuomela T, Lakanmaa M, Kiviranta E, Stefanatos R, Dufour E, Hutz B, Naudí A, Jové M, Zeb A, Vartiainen S, Matsuno-Yagi A, Yagi T, Rustin P, Pamplona R, Jacobs HT
Expression of the yeast NADH dehydrogenase Ndi1 in Drosophila confers increased lifespan independently of dietary restriction.
Proc Natl Acad Sci U S A ;107(20)9105-10, 2010

Sanz A, Fernández-Ayala DJ, Stefanatos RK, Jacobs HT
Mitochondrial ROS production correlates with, but does not directly regulate lifespan in Drosophila.
Aging (Albany NY) ;2(4)200-23, 2010

Pohjoismäki JL, Holmes JB, Wood SR, Yang MY, Yasukawa T, Reyes A, Bailey LJ, Cluett TJ, Goffart S, Willcox S, Rigby RE, Jackson AP, Spelbrink JN, Griffith JD, Crouch RJ, Jacobs HT, Holt IJ
Mammalian mitochondrial DNA replication intermediates are essentially duplex but contain extensive tracts of RNA/DNA hybrid.
J Mol Biol ;397(5)1144-55, 2010

Fernández-Ayala DJ, Chen S, Kemppainen E, O'Dell KM, Jacobs HT
Gene expression in a Drosophila model of mitochondrial disease.
PLoS One ;5(1)e8549, 2010

Dassa EP, Dufour E, Gonçalves S, Paupe V, Hakkaart GA, Jacobs HT, Rustin P
Expression of the alternative oxidase complements cytochrome c oxidase deficiency in human cells.
EMBO Mol Med 2009 ;1(1)30-6

Fukuoh A, Ohgaki K, Hatae H, Kuraoka I, Aoki Y, Uchiumi T, Jacobs HT, Kang D
DNA conformation-dependent activities of human mitochondrial RNA polymerase.
Genes Cells 2009 ;14(8)1029-42

Kemppainen E, Fernández-Ayala DJ, Galbraith LC, O'Dell KM, Jacobs HT
Phenotypic suppression of the Drosophila mitochondrial disease-like mutant tko(25t) by duplication of the mutant gene in its natural chromosomal context.
Mitochondrion 2009 ;9(5)353-63

Pohjoismäki JL, Goffart S, Tyynismaa H, Willcox S, Ide T, Kang D, Suomalainen A, Karhunen PJ, Griffith JD, Holt IJ, Jacobs HT
Human heart mitochondrial DNA is organized in complex catenated networks containing abundant four-way junctions and replication forks.
J Biol Chem 2009 ;284(32)21446-57

Rustin P, Jacobs HT
Respiratory chain alternative enzymes as tools to better understand and counteract respiratory chain deficiencies in human cells and animals.
Physiol Plant 2009 ;137(4)362-70

Dassa EP, Dufour E, Goncalves S, Jacobs HT, Rustin P
The alternative oxidase, a tool for compensating cytochrome c oxidase deficiency in human cells.
Physiol Plant 2009 ;137(4)427-34

Zanotto E, Häkkinen A, Teku G, Shen B, Ribeiro AS, Jacobs HT
NF-Y influences directionality of transcription from the bidirectional Mrps12/Sarsm promoter in both mouse and human cells.
Biochim Biophys Acta 2009 ;1789(5)432-42

Fernandez-Ayala DJ, Sanz A, Vartiainen S, Kemppainen KK, Babusiak M, Mustalahti E, Costa R, Tuomela T, Zeviani M, Chung J, O'Dell KM, Rustin P, Jacobs HT
Expression of the Ciona intestinalis alternative oxidase (AOX) in Drosophila complements defects in mitochondrial oxidative phosphorylation.
Cell Metab 2009 ;9(5)449-60

Lindsay HA, Baines R, ffrench-Constant R, Lilley K, Jacobs HT, O'Dell KM
The dominant cold-sensitive Out-cold mutants of Drosophila melanogaster have novel missense mutations in the voltage-gated sodium channel gene paralytic.
Genetics ;180(2)873-84, 2008

Zanotto E, Lehtonen V, Jacobs HT
Modulation of Mrps12/Sarsm promoter activity in response to mitochondrial stress.
Biochim Biophys Acta ;1783(12)2352-62, 2008

Hyvärinen AK, Pohjoismäki JL, Reyes A, Wanrooij S, Yasukawa T, Karhunen PJ, Spelbrink JN, Holt IJ, Jacobs HT
The mitochondrial transcription termination factor mTERF modulates replication pausing in human mitochondrial DNA.
Nucleic Acids Res 2007 ;35(19)6458-74

Toivonen JM, Walker GA, Martinez-Diaz P, Bjedov I, Driege Y, Jacobs HT, Gems D, Partridge L
No influence of Indy on lifespan in Drosophila after correction for genetic and cytoplasmic background effects.
PLoS Genet 2007 ;3(6)e95

Juhola M, Saarikoski J, Jacobs HT
On modeling of mutation probabilities.
Comput Biol Med 2007 ;37(12)1719-23

Zanotto E, Shah ZH, Jacobs HT
The bidirectional promoter of two genes for the mitochondrial translational apparatus in mouse is regulated by an array of CCAAT boxes interacting with the transcription factor NF-Y.
Nucleic Acids Res 2007 ;35(2)664-77

Yasukawa T, Reyes A, Cluett TJ, Yang MY, Bowmaker M, Jacobs HT, Holt IJ
Replication of vertebrate mitochondrial DNA entails transient ribonucleotide incorporation throughout the lagging strand.
EMBO J 2006 ;25(22)5358-71

Pohjoismäki JL, Wanrooij S, Hyvärinen AK, Goffart S, Holt IJ, Spelbrink JN, Jacobs HT
Alterations to the expression level of mitochondrial transcription factor A, TFAM, modify the mode of mitochondrial DNA replication in cultured human cells.
Nucleic Acids Res 2006 ;34(20)5815-28

Kirino Y, Yasukawa T, Marjavaara SK, Jacobs HT, Holt IJ, Watanabe K, Suzuki T
Acquisition of the wobble modification in mitochondrial tRNALeu(CUN) bearing the G12300A mutation suppresses the MELAS molecular defect.
Hum Mol Genet 2006 ;15(6)897-904

Smeitink JA, Zeviani M, Turnbull DM, Jacobs HT
Mitochondrial medicine: a metabolic perspective on the pathology of oxidative phosphorylation disorders.
Cell Metab 2006 ;3(1)9-13

Hakkaart GA, Dassa EP, Jacobs HT, Rustin P
Allotopic expression of a mitochondrial alternative oxidase confers cyanide resistance to human cell respiration.
EMBO Rep 2006 ;7(3)341-5

Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG
Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production.
Proc Natl Acad Sci U S A 2005 ;102(50)17993-8

Endo K, Noguchi Y, Ueshima R, Jacobs HT
Novel repetitive structures, deviant protein-encoding sequences and unidentified ORFs in the mitochondrial genome of the brachiopod Lingula anatina.
J Mol Evol 2005 ;61(1)36-53

Yasukawa T, Yang MY, Jacobs HT, Holt IJ
A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA.
Mol Cell 2005 ;18(6)651-62

Turner CJ, Granycome C, Hurst R, Pohler E, Juhola MK, Juhola MI, Jacobs HT, Sutherland L, Holt IJ
Systematic segregation to mutant mitochondrial DNA and accompanying loss of mitochondrial DNA in human NT2 teratocarcinoma Cybrids.
Genetics 2005 ;170(4)1879-85

Jacobs HT, Turnbull DM
Nuclear genes and mitochondrial translation: a new class of genetic disease.
Trends Genet 2005 ;21(6)312-4

Yasukawa T, Kirino Y, Ishii N, Holt IJ, Jacobs HT, Makifuchi T, Fukuhara N, Ohta S, Suzuki T, Watanabe K
Wobble modification deficiency in mutant tRNAs in patients with mitochondrial diseases.
FEBS Lett 2005 ;579(13)2948-52

Jacobs HT, Hutchin TP, Käppi T, Gillies G, Minkkinen K, Walker J, Thompson K, Rovio AT, Carella M, Melchionda S, Zelante L, Gasparini P, Pyykkö I, Shah ZH, Zeviani M, Mueller RF
Mitochondrial DNA mutations in patients with postlingual, nonsyndromic hearing impairment.
Eur J Hum Genet 2005 ;13(1)26-33

Jacobs HT, Fernández-Ayala DJ, Manjiry S, Kemppainen E, Toivonen JM, O'Dell KM
Mitochondrial disease in flies.
Biochim Biophys Acta 2004 ;1659(2-3)190-6

Smeitink JA, Jacobs HT
The Euromit meetings: an international platform for the understanding and combat of mitochondrial disease.
Biochim Biophys Acta 2004 ;1659(2-3)105-6

Andrés AM, Soldevila M, Lao O, Volpini V, Saitou N, Jacobs HT, Hayasaka I, Calafell F, Bertranpetit J
Comparative genetics of functional trinucleotide tandem repeats in humans and apes.
J Mol Evol 2004 ;59(3)329-39

Toompuu M, Levinger LL, Nadal A, Gomez J, Jacobs HT
The 7472insC mtDNA mutation impairs 5' and 3' processing of tRNA(Ser(UCN)).
Biochem Biophys Res Commun 2004 ;322(3)803-13

Rovio AT, Abel J, Ahola AL, Andres AM, Bertranpetit J, Blancher A, Bontrop RE, Chemnick LG, Cooke HJ, Cummins JM, Davis HA, Elliott DJ, Fritsche E, Hargreave TB, Hoffman SM, Jequier AM, Kao SH, Kim HS, Marchington DR, Mehmet D, Otting N, Poulton J, Ryder OA, Schuppe HC, Takenaka O, Wei YH, Wichmann L, Jacobs HT
A prevalent POLG CAG microsatellite length allele in humans and African great apes.
Mamm Genome 2004 ;15(6)492-502

Trifunovic A, Wredenberg A, Falkenberg M, Spelbrink JN, Rovio AT, Bruder CE, Bohlooly-Y M, Gidlöf S, Oldfors A, Wibom R, Törnell J, Jacobs HT, Larsson NG
Premature ageing in mice expressing defective mitochondrial DNA polymerase.
Nature 2004 ;429(6990)417-23

Toivonen JM, Manjiry S, Touraille S, Alziari S, O'Dell KM, Jacobs HT
Gene dosage and selective expression modify phenotype in a Drosophila model of human mitochondrial disease.
Mitochondrion 2003 ;3(2)83-96

Bowmaker M, Yang MY, Yasukawa T, Reyes A, Jacobs HT, Huberman JA, Holt IJ
Mammalian mitochondrial DNA replicates bidirectionally from an initiation zone.
J Biol Chem 2003 ;278(51)50961-9

Jacobs HT
Rebuttal to Pak et al.: new data, chestnuts.
Aging Cell 2003 ;2(1)19-20

Jacobs HT
Disorders of mitochondrial protein synthesis.
Hum Mol Genet 2003 ;12 Spec No 2R293-301

Jacobs HT
The mitochondrial theory of aging: dead or alive?
Aging Cell 2003 ;2(1)11-7

Holt IJ, Jacobs HT
Response: The mitochondrial DNA replication bubble has not burst.
Trends Biochem Sci 2003 ;28(7)355-6

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