TY - JOUR
T1 - Human mitochondrial pyrophosphatase
T2 - cDNA cloning and analysis of the gene in patients with mtDNA depletion syndromes
AU - Curbo, Sophie
AU - Lagier-Tourenne, Clotilde
AU - Carrozzo, Rosalba
AU - Palenzuela, Lluis
AU - Lucioli, Simona
AU - Hirano, Michio
AU - Santorelli, Filippo
AU - Arenas, Joaquin
AU - Karlsson, Anna
AU - Johansson, Magnus
PY - 2006/3
Y1 - 2006/3
N2 - Pyrophosphatases (PPases) catalyze the hydrolysis of inorganic pyrophosphate generated in several cellular enzymatic reactions. A novel human pyrophosphatase cDNA encoding a 334-amino-acid protein ≈60% identical to the previously identified human cytosolic PPase was cloned and characterized. The novel enzyme, named PPase-2, was enzymatically active and catalyzed hydrolysis of pyrophosphate at a rate similar to that of the previously identified PPase-1. A functional mitochondrial import signal sequence was identified in the N-terminus of PPase-2, which targeted the enzyme to the mitochondrial matrix. The human pyrophosphatase 2 gene (PPase-2) was mapped to chromosome 4q25 and the 1.4-kb mRNA was ubiquitously expressed in human tissues, with highest levels in muscle, liver, and kidney. The yeast homologue of the mitochondrial PPase-2 is required for mitochondrial DNA maintenance and yeast cells lacking the enzyme exhibit mitochondrial DNA depletion. We sequenced the PPA2 gene in 13 patients with mitochondrial DNA depletion syndromes (MDS) of unknown cause to determine if mutations in the PPA2 gene of these patients were associated with this disease. No pathogenic mutations were identified in the PPA2 gene of these patients and we found no evidence that PPA2 gene mutations are a common cause of MDS in humans.
AB - Pyrophosphatases (PPases) catalyze the hydrolysis of inorganic pyrophosphate generated in several cellular enzymatic reactions. A novel human pyrophosphatase cDNA encoding a 334-amino-acid protein ≈60% identical to the previously identified human cytosolic PPase was cloned and characterized. The novel enzyme, named PPase-2, was enzymatically active and catalyzed hydrolysis of pyrophosphate at a rate similar to that of the previously identified PPase-1. A functional mitochondrial import signal sequence was identified in the N-terminus of PPase-2, which targeted the enzyme to the mitochondrial matrix. The human pyrophosphatase 2 gene (PPase-2) was mapped to chromosome 4q25 and the 1.4-kb mRNA was ubiquitously expressed in human tissues, with highest levels in muscle, liver, and kidney. The yeast homologue of the mitochondrial PPase-2 is required for mitochondrial DNA maintenance and yeast cells lacking the enzyme exhibit mitochondrial DNA depletion. We sequenced the PPA2 gene in 13 patients with mitochondrial DNA depletion syndromes (MDS) of unknown cause to determine if mutations in the PPA2 gene of these patients were associated with this disease. No pathogenic mutations were identified in the PPA2 gene of these patients and we found no evidence that PPA2 gene mutations are a common cause of MDS in humans.
KW - Human pyrophosphatase
KW - Inorganic pyrophosphate
KW - Mitochondrial depletion syndrome
KW - Mitochondrial DNA
KW - Mitochondrial enzyme
KW - Mitochondrial localization
UR - http://www.scopus.com/inward/record.url?scp=32244433583&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32244433583&partnerID=8YFLogxK
U2 - 10.1016/j.ygeno.2005.09.017
DO - 10.1016/j.ygeno.2005.09.017
M3 - Article
C2 - 16300924
AN - SCOPUS:32244433583
VL - 87
SP - 410
EP - 416
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 3
ER -