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Multi-parameter Measurement of the Permeability Transition Pore Opening in Isolated Mouse Heart Mitochondria
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Microtubule disorganization affects the mitochondrial permeability transition pore in cardiac myocytes

Azumi Kumazawa1, Hideki Katoh, Daishi Nonaka

  • 1Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine.

Circulation Journal : Official Journal of the Japanese Circulation Society
|March 12, 2014
PubMed
Abstract

Insights

Microtubule disorganization impacts cardiac function by affecting mitochondrial permeability transition pore (mPTP) opening. Both MT stabilization and disruption can lead to mPTP opening, influencing cardiac myocyte health.

Area of Science:

  • Cardiovascular Biology
  • Mitochondrial Biology
  • Cellular Physiology

Background:

  • Microtubule (MT) disorganization is linked to cardiac dysfunction.
  • Understanding the MT network's role in cardiac health is crucial.

Purpose of the Study:

  • To investigate the relationship between microtubule disorganization and mitochondrial permeability transition pore (mPTP) opening in cardiac myocytes.
  • To elucidate the mechanisms by which MT network disorganization impacts cardiac function.

Main Methods:

  • Utilized permeabilized Sprague-Dawley rat myocytes.
  • Assessed mitochondrial membrane potential (ΔΨm) and mPTP opening.
  • Employed paclitaxel (MT stabilization) and nocodazole (MT disruption).
  • Investigated effects of calcium signaling and mitochondrial fusion proteins.

Main Results:

  • Both paclitaxel and nocodazole induced ΔΨm depolarization and mPTP opening in myocytes, but not isolated mitochondria.
  • Cyclosporin A inhibited these effects, suggesting mPTP involvement.
  • Paclitaxel's effect on mPTP was calcium-dependent, while nocodazole's was not.
  • Paclitaxel reduced mitofusin-2 expression and caused mitochondrial fragmentation.

Conclusions:

  • Nocodazole-induced MT disruption may sever MT-mitochondria connections, impairing mitochondrial function.
  • Paclitaxel-induced MT disorganization regulates mPTP via outer mitochondrial membrane complexes and Ca(2+)-sensitive pathways.
  • MT disorganization affects mitochondrial fusion protein mitofusin-2, contributing to cardiac dysfunction.

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