Main |
Browse Volumes |
Forthcoming Volumes |
Annals PrePrints |
Annals Extra |
E-mail Alerts |
Subscriptions & Orders |
New Proposals |
Author Guidelines |
About Annals |
Help |
 |
|
|
|
|
|
Mitochondrial Localization of Human PANK2 and Hypotheses of Secondary Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration
MONIQUE A. JOHNSONa,
YIEN MING KUOb,
SHAWN K. WESTAWAYa,
SUSAN M. PARKERa,
KATHERINE H. L. CHINGa,
JANE GITSCHIERb AND
SUSAN J. HAYFLICKa,c
aDepartment of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, Oregon, USA
bHoward Hughes Medical Institute and Departments of Medicine and Pediatrics, University of California, San Francisco, California, USA
cDepartments of Pediatrics and Neurology, School of Medicine, Oregon Health and Science University, Portland, Oregon, USA
Address for correspondence: Susan J. Hayflick, Department of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, OR 97239. Voice: 503-494-6866; fax: 503-494-4411. hayflick{at}ohsu.ed
Ann N.Y. Acad. Sci. 1012: 282-298 (2004).
Mutations in the pantothenate kinase 2 gene ( PANK2) lead to pantothenate kinase-associated neurodegeneration (PKAN, formerly Hallervorden-Spatz syndrome). This neurodegenerative disorder is characterized by iron accumulation in the basal ganglia. Pantothenate kinase is the first enzyme in the biosynthesis of coenzyme A from pantothenate (vitamin B 5). PANK2, one of four human pantothenate kinase genes, is uniquely predicted to be targeted to mitochondria. We demonstrate mitochondrial localization of PANK2 and speculate on mechanisms of secondary iron accumulation in PKAN. Furthermore, PANK2 uses an unconventional translational start codon, CUG, which is polymorphic in the general population. The variant sequence, CAG (allele frequency: 0.05), leads to skipping of the mitochondrial targeting signal and cytosolic localization of PANK2. This common variant may cause mitochondrial dysfunction and impart susceptibility to late-onset neurodegenerative disorders with brain iron accumulation, including Parkinson's disease.
Key Words: pantothenate kinase • PKAN • Hallervorden-Spatz syndrome • mitochondrial localization • CoA • brain iron
This article has been cited by other articles:
|
|
|
|
 
K. Shinzawa, H. Sumi, M. Ikawa, Y. Matsuoka, M. Okabe, S. Sakoda, and Y. Tsujimoto
Neuroaxonal Dystrophy Caused by Group VIA Phospholipase A2 Deficiency in Mice: A Model of Human Neurodegenerative Disease
J. Neurosci.,
February 27, 2008;
28(9):
2212 - 2220.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kazek, E. Jamroz, M. Gencik, A. Jezela Stanek, E. Marszal, and K. Wojaczynska-Stanek
A Novel PANK2 Gene Mutation: Clinical and Molecular Characteristics of Patients Short Communication
J Child Neurol,
November 1, 2007;
22(11):
1256 - 1259.
[Abstract]
[PDF]
|
|
|
|
|
|
|
B. S. Hong, G. Senisterra, W. M. Rabeh, M. Vedadi, R. Leonardi, Y.-M. Zhang, C. O. Rock, S. Jackowski, and H.-W. Park
Crystal Structures of Human Pantothenate Kinases: INSIGHTS INTO ALLOSTERIC REGULATION AND MUTATIONS LINKED TO A NEURODEGENERATION DISORDER
J. Biol. Chem.,
September 21, 2007;
282(38):
27984 - 27993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Boddaert, K. H. Le Quan Sang, A. Rotig, A. Leroy-Willig, S. Gallet, F. Brunelle, D. Sidi, J.-C. Thalabard, A. Munnich, and Z. I. Cabantchik
Selective iron chelation in Friedreich ataxia: biologic and clinical implications
Blood,
July 1, 2007;
110(1):
401 - 408.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Leonardi, C. O. Rock, S. Jackowski, and Y.-M. Zhang
Activation of human mitochondrial pantothenate kinase 2 by palmitoylcarnitine
PNAS,
January 30, 2007;
104(5):
1494 - 1499.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. W. Lee, J. K Andersen, and D. Kaur
Iron dysregulation and neurodegeneration: the molecular connection.
Mol. Interv.,
April 1, 2006;
6(2):
89 - 97.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-M. Zhang, C. O. Rock, and S. Jackowski
Biochemical Properties of Human Pantothenate Kinase 2 Isoforms and Mutations Linked to Pantothenate Kinase-associated Neurodegeneration
J. Biol. Chem.,
January 6, 2006;
281(1):
107 - 114.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-M. Zhang, C. O. Rock, and S. Jackowski
Feedback Regulation of Murine Pantothenate Kinase 3 by Coenzyme A and Coenzyme A Thioesters
J. Biol. Chem.,
September 23, 2005;
280(38):
32594 - 32601.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-M. Kuo, J. L. Duncan, S. K. Westaway, H. Yang, G. Nune, E. Y. Xu, S. J. Hayflick, and J. Gitschier
Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia
Hum. Mol. Genet.,
January 1, 2005;
14(1):
49 - 57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
