The respiratory chain inhibitor rotenone affects peroxisomal dynamics via its microtubule-destabilising activity

The respiratory chain inhibitor rotenone affects peroxisomal dynamics via its... Peroxisomes and mitochondria in mammalian cells are closely linked subcellular organelles, which maintain a redox-sensitive relationship. Their interplay and role in ROS signalling are supposed to impact on age-related and degenerative disorders. Whereas the generation of peroxisome-derived oxidative stress can affect mitochondrial morphology and function, little is known about the impact of mitochondria-derived oxidative stress on peroxisomes. Here, we investigated the effect of the mitochondrial complex I inhibitor rotenone on peroxisomal and mitochondrial membrane dynamics. We show that rotenone treatment of COS-7 cells alters peroxisome morphology and distribution. However, this effect is related to its microtubule-destabilising activity rather than to the generation of oxidative stress. Rotenone also induced alterations in mitochondrial morphology, which—in contrast to its effect on peroxisomes—were dependent on the generation of ROS but independent of its microtubule-active properties. The importance of our findings for the peroxisome-mitochondria redox relationship and the interpretation of in cellulo and in vivo studies with rotenone, which is widely used to study Parkinson’s disease, are discussed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Histochemistry and Cell Biology Springer Journals

The respiratory chain inhibitor rotenone affects peroxisomal dynamics via its microtubule-destabilising activity

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Publisher
Springer Berlin Heidelberg
Copyright
Copyright © 2017 by The Author(s)
Subject
Biomedicine; Biomedicine, general; Cell Biology; Biochemistry, general; Developmental Biology
ISSN
0948-6143
eISSN
1432-119X
D.O.I.
10.1007/s00418-017-1577-1
Publisher site
See Article on Publisher Site

Abstract

Peroxisomes and mitochondria in mammalian cells are closely linked subcellular organelles, which maintain a redox-sensitive relationship. Their interplay and role in ROS signalling are supposed to impact on age-related and degenerative disorders. Whereas the generation of peroxisome-derived oxidative stress can affect mitochondrial morphology and function, little is known about the impact of mitochondria-derived oxidative stress on peroxisomes. Here, we investigated the effect of the mitochondrial complex I inhibitor rotenone on peroxisomal and mitochondrial membrane dynamics. We show that rotenone treatment of COS-7 cells alters peroxisome morphology and distribution. However, this effect is related to its microtubule-destabilising activity rather than to the generation of oxidative stress. Rotenone also induced alterations in mitochondrial morphology, which—in contrast to its effect on peroxisomes—were dependent on the generation of ROS but independent of its microtubule-active properties. The importance of our findings for the peroxisome-mitochondria redox relationship and the interpretation of in cellulo and in vivo studies with rotenone, which is widely used to study Parkinson’s disease, are discussed.

Journal

Histochemistry and Cell BiologySpringer Journals

Published: May 18, 2017

References

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