Research article

Evidence for a mitochondrial localization of the retinoblastoma protein

Ioana Ferecatu^1,2 , Nathalie Le Floch^1,2 , Marie Bergeaud¹ , Aida Rodríguez-Enfedaque^1,2 , Vincent Rincheval¹ , Lisa Oliver³ , François M Vallette³ , Bernard Mignotte^1,2 and Jean-Luc Vayssière^1,2

¹  Laboratoire de génétique et biologie cellulaire – CNRS UMR 8159, Université de Versailles Saint-Quentin-en-Yvelines, Versailles, France

²  Laboratoire de génétique moléculaire et physiologique, Ecole Pratique des Hautes Etudes, Versailles, France

³  INSERM U601, Faculté de Médecine – Université de Nantes, Nantes, France

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BMC Cell Biology 2009, 10:50doi:10.1186/1471-2121-10-50

Published:	25 June 2009

Abstract

Background

The retinoblastoma protein (Rb) plays a central role in the regulation of cell cycle, differentiation and apoptosis. In cancer cells, ablation of Rb function or its pathway is a consequence of genetic inactivation, viral oncoprotein binding or deregulated hyperphosphorylation. Some recent data suggest that Rb relocation could also account for the regulation of its tumor suppressor activity, as is the case for other tumor suppressor proteins, such as p53.

Results

In this reported study, we present evidence that a fraction of the total amount of Rb protein can localize to the mitochondria in proliferative cells taken from both rodent and human cells. This result is also supported by the use of Rb siRNAs, which substantially reduced the amount of mitochondrial Rb, and by acellular assays, in which [³⁵S]-Methionine-labeled Rb proteins bind strongly to mitochondria isolated from rat liver. Moreover, endogenous Rb is found in an internal compartment of the mitochondria, within the inner-membrane. This is consistent with the protection of Rb from alkaline treatment, which destroys any interaction of proteins that are weakly bound to mitochondria.

Conclusion

Although a few data regarding an unspecific cytosolic localization of Rb protein have been reported for some tumor cells, our results are the first evidence of a mitochondrial localization of Rb. The mitochondrial localization of Rb is observed in parallel with its classic nuclear location and paves the way for the study of potential as-yet-unknown roles of Rb at this site.