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Human Molecular Genetics Advance Access published online on January 31, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl006
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© The Author 2006. Published by Oxford University Press. All rights reserved
Received October 28, 2005
Revised January 25, 2006
Accepted January 25, 2006

Article

Parkin enhances mitochondrial biogenesis in proliferating cells

Yukiko Kuroda 1, Takao Mitsui 1 *, Makoto Kunishige 1, Masayuki Shono 2, Masashi Akaike 1, Hiroyuki Azuma 1, and Toshio Matsumoto 1

1 Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan
2 General Laboratory for Medical Research, University of Tokushima Graduate School of Medicine, Kuramoto-3, Tokushima 770-8503, Japan

* To whom correspondence should be addressed.
Takao Mitsui, E-mail: tmitsui{at}clin.med.tokushima-u.ac.jp


  Abstract

We describe a novel function of parkin, a RING protein, which is elaborately involved in mitochondrial biogenesis. Parkin was located within the mitochondrial organelle of proliferating cells. Anti-proliferative treatments released parkin from mitochondria to cytosol. Results of pharmacological treatments indicate that parkin was released from mitochondria when permeability transition pore was opened. The extra-mitochondrial localization was also observed in differentiated cells. In proliferating cells, transcription and replication of mitochondrial DNA was enhanced by parkin overexpression and attenuated by parkin suppression with siRNA. Parkin was associated with mitochondrial transcription factor A (TFAM) and enhanced TFAM-mediated mitochondrial transcription. These results indicate that parkin is involved in the regulation of mitochondrial transcription/replicaion other than the ubiquitin-mediated protein degradation system in proliferating cells. (119 words).


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