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Gluing the respiratory chain together. Cardiolipin is required for supercomplex formation in the inner mitochondrial

Mei Zhang1, Eugenia Mileykovskaya, William Dowhan

  • 1Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225, USA.

The Journal of Biological Chemistry
|October 5, 2002
PubMed

Insights

Cardiolipin (CL) is crucial for mitochondrial respiratory chain organization. Lowering CL levels disrupts the supercomplex formation of cytochrome bc1 (Complex III) and cytochrome c oxidase (Complex IV) in yeast.

Area of Science:

  • Mitochondrial biology
  • Biochemistry
  • Cellular respiration

Background:

  • Cytochrome bc1 complex (Complex III) and cytochrome c oxidase complex (Complex IV) are essential multisubunit homodimers in the mitochondrial respiratory chain.
  • These complexes associate to form a supercomplex, visualized by blue native polyacrylamide gel electrophoresis.
  • Both complexes require cardiolipin (CL) for their function.

Purpose of the Study:

  • To investigate the role of cardiolipin (CL) in the higher-order organization of mitochondrial respiratory chain complexes.
  • To determine if CL is essential for the formation of the Complex III-IV supercomplex.

Main Methods:

  • Utilized a crd1Δ yeast strain lacking cardiolipin synthase to study the effects of CL deficiency.
  • Employed blue native polyacrylamide gel electrophoresis to analyze the assembly of respiratory chain complexes.
  • Controlled in vivo CL levels using doxycycline-inducible expression of the CRD1 gene.

Main Results:

  • In yeast lacking CL (crd1Δ strain), approximately 90% of Complexes III and IV existed as individual homodimers, with minimal supercomplex formation.
  • Wild-type cells exclusively displayed the supercomplex.
  • Intermediate CL levels resulted in a mixture of individual homodimers (30%) and supercomplex (70%).

Conclusions:

  • Cardiolipin plays a critical role in the higher-order organization and supercomplex formation of mitochondrial respiratory chain components.
  • CL is essential for maintaining the structural integrity of the Complex III-IV supercomplex.

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