The respiratory chain inhibitor rotenone affects peroxisomal dynamics via its microtubule-destabilising activity.
Josiah B. Passmore,Sónia Pinho,Maria Gomez-Lazaro,Maria Gomez-Lazaro,Michael Schrader,Michael Schrader +5 more
TLDR
It is shown that rotenone treatment of COS-7 cells alters peroxisome morphology and distribution, but this effect is related to its microtubule-destabilising activity rather than to the generation of oxidative stress.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.read more
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Journal ArticleDOI
Peroxisome biogenesis, membrane contact sites, and quality control
TL;DR: The current status of the different co‐existing modes of biogenesis of peroxisomal membrane proteins demonstrating the fascinating adaptability in their targeting and sorting pathways is reviewed.
Journal ArticleDOI
Biological Implications of Differential Expression of Mitochondrial-Shaping Proteins in Parkinson's Disease.
TL;DR: With the bioinformatics approach using the data on the modified proteins in Parkinson’s disease patients, the alteration of mitochondrial-shaping proteins to modifications of crucial cellular pathways affected in this disease are related.
Journal ArticleDOI
A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes
Inês G. Castro,David M. Richards,Jeremy Metz,Joseph L. Costello,Josiah B. Passmore,Tina A. Schrader,Ana Gouveia,Daniela Ribeiro,Michael Schrader +8 more
TL;DR: A role for Mitochondrial Rho GTPase 1 (MIRO1) is identified as an adaptor for microtubule‐dependent peroxisome motility in mammalian cells and it is demonstrated that MIRO1‐mediated pulling forces contribute to perox isome membrane elongation and proliferation in cellular models of peroxISome disease.
Journal ArticleDOI
Rotenone: from modelling to implication in Parkinson's disease.
Khaled Radad,Khaled Radad,Mubarak Al-Shraim,Ahmed Al-Emam,Ahmed Al-Emam,Feixue Wang,Barbara Kranner,Wolf-Dieter Rausch,Rudolf Moldzio +8 more
TL;DR: The current general review aimed to address recent advances in the hazards of the environmental applications of rotenone and discuss the updates on the roten one model of PD and whether it is implicated in the etiopathogenesis of the disease.
Journal ArticleDOI
Mitochondrial toxicity of nanomaterials
TL;DR: The mitochondrial toxicity of NMs is reviewed and a scientific basis for the contribution of mitochondria to the toxicological effects of different NMs along with approaches to reduce mitochondrial and, consequently, overall toxicity ofNMs is provided.
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