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Apoptotic microtubule network organization and maintenance depend on high cellular ATP levels and energized

Manuel Oropesa1, Mario de la Mata, Juan Garrido Maraver

  • 1Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-Consejo Superior de Investigaciones Científicas, Carretera de Utrera Km. 1, Seville, Spain.

Apoptosis : an International Journal on Programmed Cell Death
|February 12, 2011
PubMed

Insights

The apoptotic microtubule network (AMN) maintains cell integrity during programmed cell death. AMN stabilization prevents plasma membrane damage, highlighting its crucial role in apoptosis.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Apoptosis Research

Background:

  • The microtubule cytoskeleton reorganizes during apoptosis, forming a cortical structure crucial for cell morphology and plasma membrane integrity.
  • The maintenance mechanisms of the apoptotic microtubule network (AMN) during apoptosis remain unclear.

Purpose of the Study:

  • To investigate the role of cellular energy status and mitochondrial function in maintaining the AMN during apoptosis.
  • To elucidate the relationship between AMN integrity, mitochondrial membrane potential, and plasma membrane permeability.

Main Methods:

  • Induction of apoptosis using camptothecin (CPT) in human H460 and porcine LLCPK-1α cells.
  • Assessment of ATP levels, mitochondrial membrane potential, and intracellular calcium.
  • Live-cell imaging of microtubule dynamics and mitochondrial membrane potential.
  • Evaluation of plasma membrane permeability via LDH release.
  • Pharmacological stabilization of AMN using taxol and assessment of ATP synthase activity.

Main Results:

  • AMN organization correlated with high ATP levels and hyperpolarized mitochondria; AMN dismantled with low ATP and depolarized mitochondria.
  • Mitochondrial depolarization led to increased plasma membrane permeability (LDH release) and calcium influx.
  • AMN stabilization with taxol preserved plasma membrane integrity despite mitochondrial depolarization.
  • ATP synthase appeared to operate in reverse mode during apoptosis, contributing to high ATP levels.

Conclusions:

  • The apoptotic microtubule network (AMN) is essential for maintaining plasma membrane integrity during apoptosis.
  • AMN stability is dependent on cellular energy levels and mitochondrial function.
  • Targeting AMN may offer therapeutic strategies for preventing secondary necrosis and associated damage.

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