QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 6 March 2007
doi: 10.1242/jcs.03418

This Article Figures Only Full Text Full Text (PDF) Supplementary Material All Versions of this Article: jcs.03418v1 120/7/1178    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zunino, R. Articles by McBride, H. M. Search for Related Content PubMed PubMed Citation Articles by Zunino, R. Articles by McBride, H. M.

The SUMO protease SENP5 is required to maintain mitochondrial morphology and function

¹ University of Ottawa Heart Institute, Rm H445A, 40 Ruskin Street, Ottawa, Ontario, K1Y 4W7, Canada
² Ontario Genomics Innovation Centre, Ottawa Health Research Institute, 501 Smyth, Ottawa, Ontario K1H 8L6, Canada

^* Author for correspondence (e-mail: hmcbride{at}ottawaheart.ca)

Accepted 23 January 2007

Mitochondria are dynamic organelles that undergo regulated fission and fusion events that are essential to maintain metabolic stability. We previously demonstrated that the mitochondrial fission GTPase DRP1 is a substrate for SUMOylation. To further understand how SUMOylation impacts mitochondrial function, we searched for a SUMO protease that may affect mitochondrial dynamics. We demonstrate that the cytosolic pool of SENP5 catalyzes the cleavage of SUMO1 from a number of mitochondrial substrates. Overexpression of SENP5 rescues SUMO1-induced mitochondrial fragmentation that is partly due to the downregulation of DRP1. By contrast, silencing of SENP5 results in a fragmented and altered morphology. DRP1 was stably mono-SUMOylated in these cells, suggesting that SUMOylation leads to increased DRP1 mediated fission. In addition, the reduction of SENP5 levels resulted in a significant increase in the production of free radicals. Reformation of the mitochondrial tubules by expressing the dominant interfering DRP1 or by RNA silencing of endogenous DRP1 protein rescued both the morphological aberrations and the increased production of ROS induced by downregulation of SENP5. These data demonstrate the importance of SENP5 as a new regulator of SUMO1 proteolysis from mitochondrial targets, impacting mitochondrial morphology and metabolism.

Key words: DRP1, SUMO, SENP5, Protease, Mitochondrial fission, ROS

Related articles in JCS:

SUMO wrestling in mitochondria

JCS 2007 120: 703. [Full Text]  

This article has been cited by other articles:

				D.-F. Suen, K. L. Norris, and R. J. Youle Mitochondrial dynamics and apoptosis Genes & Dev., June 15, 2008; 22(12): 1577 - 1590. [Abstract] [Full Text] [PDF]

				S. Gandre-Babbe and A. M. van der Bliek The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian Cells Mol. Biol. Cell, June 1, 2008; 19(6): 2402 - 2412. [Abstract] [Full Text] [PDF]

				A. C. Poole, R. E. Thomas, L. A. Andrews, H. M. McBride, A. J. Whitworth, and L. J. Pallanck The PINK1/Parkin pathway regulates mitochondrial morphology PNAS, February 5, 2008; 105(5): 1638 - 1643. [Abstract] [Full Text] [PDF]

				J. Chen, X. Shi, R. Padmanabhan, Q. Wang, Z. Wu, S. C. Stevenson, M. Hild, D. Garza, and H. Li Identification of novel modulators of mitochondrial function by a genome-wide RNAi screen in Drosophila melanogaster Genome Res., January 1, 2008; 18(1): 123 - 136. [Abstract] [Full Text] [PDF]