Laurie S. Kaguni
Research Interests
The mitochondrion is the energy producing organelle in the cell, and
the only organelle in animal cells besides the nucleus that contains its
own chromosome. Maintenance of mitochondrial function requires the
replication and expression of the mitochondrial genome. 
Remarkably, not a
single gene involved in mitochondrial molecular biology is encoded in the
compact mitochondrial genome: all of the protein machinery for
replication, transcription, and translation (and DNA repair functions) is
encoded in the nucleus, and the relevant proteins must be imported into
the mitochondrion.
Our research is centered around understanding
the molecular mechanisms involved in the replication and expression of the
mitochondrial DNA genome and their regulation. Our experimental approach
is to employ a combination of biochemical and molecular genetic methods
toward the development of in vitro and transgenic systems from
Drosophila. Efforts are focused in two major areas. The first is
the identification, molecular cloning and structure-function analysis of
nuclear-encoded proteins involved in mitochondrial function. These
currently include: the mitochondrial DNA polymerase which was purified and
cloned for the first time in our laboratory, mitochondrial single-stranded
DNA-binding protein (mtSSB), mtDNA helicase, mtDNA sequence-specific
binding proteins involved in regulation of replication and transcription,
protein components of the mitochondrial chromosome, and mtRNA polymerase.
A second research effort is on elucidation of the organization,
structure and regulated expression of the nuclear genes encoding
mitochondrial proteins and in particular, those involved in mitochondrial
molecular biology. MORE
Recent Publications
Oliveira MT, Kaguni LS. 2011. Reduced Stimulation of Recombinant DNA Polymerase gamma and Mitochondrial DNA (mtDNA) Helicase by Variants of Mitochondrial Single-stranded DNA-binding Protein (mtSSB) Correlates with Defects in mtDNA Replication in Animal Cells. J. Biol. Chem. 286:40649-40658. Link to article
Euro L, Farnum GA, Palin E, Suomalainen A, Kaguni LS. 2011. Clustering of Alpers disease mutations and catalytic defects in biochemical variants reveal new features of molecular mechanism of the human mitochondrial replicase, Pol γ. Nucl. Acids Res. Nov 1;39(21):9072-84. Link to article
Oliveira MT, Kaguni LS. 2010. Functional Roles of the N- and C-Terminal Regions of the Human Mitochondrial Single-Stranded DNA-Binding Protein. PLoS One. 2010 Oct 28;5(10):e15379. Link to article
Matsushima Y, Goto Y, Kaguni LS. 2010. Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM). Proc Natl Acad Sci U S A. 107(43):18410-5. Link to article
Makowska-MM Grzyska, TD Ziebarth, LS Kaguni. 2010. Physical analysis of recombinant forms of the human mitochondrial DNA helicase. Methods. Aug;51 411-415. Link to article.
Ziebarth TD, Gonzalez-Soltero R, Makowska-Grzyska MM, Nunez-Ramirez R, Carazo JM, Kaguni LS. 2010. Dynamic effects of cofactors and DNA on the oligomeric state of human mitochondrial DNA helicase. J Biol Chem. May 7;285(19):14639-47. Link to article
Dallmann HG, Fackelmayer OJ, Tomer G, Chen J, Wiktor-Becker A, Ferrara T, Pope C, Oliveira MT, Burgers PM, Kaguni LS, McHenry CS. 2010. Parallel Multiplicative Target Screening against Divergent Bacterial Replicases: Identification of Specific Inhibitors with Broad Spectrum Potential. Biochemistry. Mar 23;49(11):2551-62. Link to article
Oliveira MT, Garesse R, Kaguni LS. 2010. Animal models of mitochondrial DNA transactions in disease and ageing. Exp Gerontol. Aug;45(7-8):489-502. Link to article
Palin EJ, Lesonen A, Farr CL, Euro L, Suomalainen A, Kaguni LS. 2010. Functional analysis of H. sapiens DNA polymerase gamma spacer mutation W748S with and without common variant E1143G. Biochim Biophys Acta. Jun;1802(6):545-51 Link to article
Baqri RM, Turner BA, Rheuben MB, Hammond BD, Kaguni LS, Miller KE. 2009. Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. PLoS One. Nov 17;4(11):e7874. Link to article
Matsushima Y, Kaguni LS. 2009. Functional importance of the conserved N-terminal domain of the mitochondrial replicative DNA helicase, Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1787(5):290-5. Link to article
