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Miro1-mediated mitochondrial positioning supports subcellular redox status
- Source :
- Redox Biology, Redox Biology, Vol 38, Iss, Pp 101818-(2021)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Mitochondria are strategically trafficked throughout the cell by the action of microtubule motors, the actin cytoskeleton and adapter proteins. The intracellular positioning of mitochondria supports subcellular levels of ATP, Ca2+ and reactive oxygen species (ROS, i.e. hydrogen peroxide, H2O2). Previous work from our group showed that deletion of the mitochondrial adapter protein Miro1 leads to perinuclear clustering of mitochondria, leaving the cell periphery devoid of mitochondria which compromises peripheral energy status. Herein, we report that deletion of Miro1 significantly restricts subcellular H2O2 levels to the perinuclear space which directly affects intracellular responses to elevated mitochondrial ROS. Using the genetically encoded H2O2-responsive fluorescent biosensor HyPer7, we show that the highest levels of subcellular H2O2 map to sites of increased mitochondrial density. Deletion of Miro1 or disruption of microtubule dynamics with Taxol significantly reduces peripheral H2O2 levels. Following inhibition of mitochondrial complex 1 with rotenone we observe elevated spikes of H2O2 in the cell periphery and complementary oxidation of mitochondrial peroxiredoxin 3 (PRX3) and cytosolic peroxiredoxin 2 (PRX2). Conversely, in cells lacking Miro1, rotenone did not increase peripheral H2O2 or PRX2 oxidation but rather lead to increased nuclear H2O2 and an elevated DNA-damage response. Lastly, local levels of HyPer7 oxidation correlate with the size and abundance of focal adhesions (FAs) in MEFs and cells lacking Miro1 have significantly smaller focal adhesions and reduced phosphorylation levels of vinculin and p130Cas compared to Miro1+/+ MEFs. Together, we present evidence that the intracellular distribution of mitochondria influences subcellular H2O2 levels and local cellular responses dependent on mitochondrial ROS.<br />Graphical abstract Image 1
- Subjects :
- 0301 basic medicine
Mitochondrial ROS
Mitochondrial trafficking
Clinical Biochemistry
Peroxiredoxin 2
Mitochondrion
Biochemistry
Focal adhesion
Mitochondrial Proteins
03 medical and health sciences
0302 clinical medicine
Cell migration
lcsh:QH301-705.5
lcsh:R5-920
Chemistry
Organic Chemistry
Hydrogen Peroxide
Actin cytoskeleton
Cell biology
Mitochondria
Cytosol
030104 developmental biology
lcsh:Biology (General)
Miro1
lcsh:Medicine (General)
Peroxiredoxin
Reactive Oxygen Species
Oxidation-Reduction
030217 neurology & neurosurgery
Intracellular
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 22132317
- Volume :
- 38
- Database :
- OpenAIRE
- Journal :
- Redox Biology
- Accession number :
- edsair.doi.dedup.....1e5b1cf7ff4dfe06dff998369d2f1f9b