Deletion of mt DNA disrupts mitochondrial function and structure, but not biogenesis

Ekhson Holmuhamedov, Arshad Jahangir, Martin Bienengraeber, Lionel D. Lewis, Andre Terzic

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

The role of nuclear DNA (n DNA)-encoded proteins in the regulation of mitochondrial fission and fusion has been documented, yet the role of mitochondrial DNA ( mt DNA) and encoded proteins in mitochondrial biogenesis remains unknown. Long-term treatment of a lymphoblastoid cell line Molt-4 with ethidium bromide generated mt DNA-deficient rho0 mutants. Depletion of mt DNA in rho0 cells produced functional and morphological changes in mitochondria without affecting the nuclear genome and encoded proteins. Indeed, the gene encoding subunit II of mitochondrial cytochrome c oxidase (COX II), a prototypical mitochondrial gene, was reduced in rho0 mutants blunting the activity of mitochondrial cytochrome c oxidase. Yet, the amount of the nuclear β-actin gene and the activity of citrate synthase, a mitochondrial matrix enzyme encoded by n DNA, remained unaffected in rho0 cells. Loss of mt DNA in rho0 cells was associated with significant distortion of mitochondrial structure, decreased electron density of the matrix and disorganized inner and outer membranes, resulting in the appearance of 'ghost-like' mitochondria. However, the number of mitochondria-like structures was not significantly different between mt DNA-deficient and parental cells. Thus, we conclude that cells lacking mt DNA still generate mitochondrial scaffolds, albeit with aberrant function.

Original languageEnglish (US)
Pages (from-to)13-19
Number of pages7
JournalMitochondrion
Volume3
Issue number1
DOIs
StatePublished - Aug 1 2003

Keywords

  • Mitochondrial DNA
  • Mitochondriogenesis
  • Molt-4
  • rho cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cell Biology

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