Mitochondrial binding of α-enolase stabilizes mitochondrial membrane: its role in doxorubicin-induced cardiomyocyte apoptosis

Arch Biochem Biophys. 2014 Jan 15;542:46-55. doi: 10.1016/j.abb.2013.12.008. Epub 2013 Dec 17.

Abstract

α-Enolase is a metabolic enzyme in the catabolic glycolytic pathway. In eukaryotic cells, the subcellular compartmentalization of α-enolase as well as its multifaceted functions has been identified. Here, we report that α-enolase is a regulator of cardiac mitochondria; it partially located in the mitochondria of rat cardiomyocytes. Doxorubicin treatment displaced α-enolase from mitochondria, accompanied by activation of mitochondrial cell death pathway. Furthermore, in isolated mitochondria, recombinant α-enolase significantly alleviated Ca(2+)-induced loss of membrane potential, swelling of matrix and permeabilization of membrane. In contrast, mitochondria from α-enolase knockdown H9c2 myoblasts underwent more severe membrane depolarization and swelling after Ca(2+) stimulation. In addition, α-enolase was further identified to interact with voltage dependent anion channel 1 in the outer membrane of mitochondria, which was weakened by doxorubicin. Collectively, the present study indicates that mitochondria-located α-enolase has a beneficial role in stabilizing mitochondrial membrane. In cardiomyocytes, the displacement of α-enolase from mitochondria by doxorubicin may involve in activation of the intrinsic cell death pathway.

Keywords: Apoptosis; Cardiomyocytes; Doxorubicin; Mitochondria; Voltage dependent anion channel; α-Enolase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Calcium / metabolism
  • Cytoplasm / drug effects
  • Cytoplasm / metabolism
  • Doxorubicin / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / drug effects*
  • Myocytes, Cardiac / cytology*
  • Myocytes, Cardiac / drug effects
  • Permeability / drug effects
  • Phosphopyruvate Hydratase / metabolism*
  • Phosphopyruvate Hydratase / pharmacology
  • Protein Transport / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Voltage-Dependent Anion Channel 1 / metabolism

Substances

  • Recombinant Proteins
  • Doxorubicin
  • Voltage-Dependent Anion Channel 1
  • Phosphopyruvate Hydratase
  • Calcium