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

Histochemistry and Cell Biology
Josiah B PassmoreMichael Schrader

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.

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Citations

Dec 12, 2018·EMBO Reports·Jean-Claude FarréSuresh Subramani
Nov 25, 2019·Histochemistry and Cell Biology·Douglas J Taatjes, Jürgen Roth
Jul 20, 2017·Histochemistry and Cell Biology·Douglas J Taatjes, Jürgen Roth
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Afsoon S AzadiMichael Schrader
Nov 13, 2019·The Science of the Total Environment·Daming WuTing Zhang
Jan 18, 2021·Physiological Research·M PokusaA Kráľová-Trančíková

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Methods Mentioned

BETA
electrophoresis
Protein Assay
acetylation

Software Mentioned

MetaMorph
GraphPad Prism

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