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
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
Oliveira MT, Kaguni LS. 2009. Comparative Purification Strategies for Drosophila and Human Mitochondrial DNA Replication Proteins: DNA Polymerase gamma and Mitochondrial Single-Stranded DNA-Binding Protein. Methods Mol Biol.554:37-58.
Ziebarth TD, Kaguni LS. 2009. Purification strategy for recombinant forms of the human mitochondrial DNA helicase. Methods Mol Biol. 554:121-6.
Weinreb V, Li L, Campbell CL, Kaguni LS, Carter CW Jr. 2009. Mg2+-assisted catalysis by B. stearothermophilus TrpRS is promoted by allosteric effects. Structure. 17(7):952-64.
Matsushima Y, Farr CL, Fan L, Kaguni LS. 2008. Physiological and biochemical defects in carboxyl-terminal mutants of mitochondrial DNA helicase. J Biol Chem. 283(35):23964-71.
Adan C, Matsushima Y, Hernandez-Sierra R, Marco-Ferreres R, Fernandez-Moreno MA, Gonzalez-Vioque E, Calleja M, Aragon JJ, Kaguni LS, Garesse R. 2008. Mitochondrial transcription factor B2 is essential for metabolic function in Drosophila melanogaster development. J Biol Chem. 283(18):12333-42.
Martinez-Azorin F, Calleja M, Hernandez-Sierra R, Farr CL, Kaguni LS, Garesse R. 2008. Overexpression of the catalytic core of mitochondrial DNA polymerase in the nervous system of Drosophila melanogaster reduces median life span by inducing mtDNA depletion. J Neurochem. 105(1):165-76.
Fernandez-Moreno MA, Farr CL, Kaguni LS. 2007. Garesse R. Drosophila melanogaster as a model system to study mitochondrial biology. Methods Mol Biol. 372:33-49.
Matsushima Y, Adan C, Garesse R, Kaguni LS. 2007. Functional analysis by inducible RNA interference in Drosophila melanogaster. Methods Mol Biol. 372:207-17.
Ziebarth TD, Farr CL, Kaguni LS. 2007. Modular architecture of the hexameric human mitochondrial DNA helicase. J Mol Biol. Apr 13; 367(5): 1382-91. Epub 2007 Feb 7.
Matsushima Y, Kaguni LS. 2007. Differential phenotypes of active site and human autosomal dominant progressive external ophthalmoplegia mutations in Drosophila mitochondrial DNA helicase expressed in Schneider cells. J Biol Chem. Mar 30; 282 (13):9436-44. Epub 2007 Jan 31.
Sanchez-Martinez A, Luo N, Clemente P, Adan C, Hernandez-Sierra R, Ochoa P, Fernandez-Moreno MA, Kaguni LS, Garesse R. 2006. Modeling human mitochondrial diseases in flies. Biochim Biophys Acta. Sep-Oct; 1757(9-10) :1190-8. Epub 2006 May 13. Review.
Fan L, Kim S, Farr CL, Schaefer KT, Randolph KM, Tainer JA, Kaguni LS. 2006. A novel processive mechanism for DNA synthesis revealed by structure, modeling and mutagenesis of the accessory subunit of human mitochondrial DNA polymerase. J Mol Biol. May 19; 358(5): 1229-43. Epub 2006 Mar 15.